Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase.
A glycoprotein that is important in the activation of CLASSICAL COMPLEMENT PATHWAY. C4 is cleaved by the activated COMPLEMENT C1S into COMPLEMENT C4A and COMPLEMENT C4B.
The sequential activation of serum COMPLEMENT PROTEINS to create the COMPLEMENT MEMBRANE ATTACK COMPLEX. Factors initiating complement activation include ANTIGEN-ANTIBODY COMPLEXES, microbial ANTIGENS, or cell surface POLYSACCHARIDES.
A subcomponent of complement C1, composed of six copies of three polypeptide chains (A, B, and C), each encoded by a separate gene (C1QA; C1QB; C1QC). This complex is arranged in nine subunits (six disulfide-linked dimers of A and B, and three disulfide-linked homodimers of C). C1q has binding sites for antibodies (the heavy chain of IMMUNOGLOBULIN G or IMMUNOGLOBULIN M). The interaction of C1q and immunoglobulin activates the two proenzymes COMPLEMENT C1R and COMPLEMENT C1S, thus initiating the cascade of COMPLEMENT ACTIVATION via the CLASSICAL COMPLEMENT PATHWAY.
Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue.
A component of the CLASSICAL COMPLEMENT PATHWAY. C2 is cleaved by activated COMPLEMENT C1S into COMPLEMENT C2B and COMPLEMENT C2A. C2a, the COOH-terminal fragment containing a SERINE PROTEASE, combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
The large fragment formed when COMPLEMENT C4 is cleaved by COMPLEMENT C1S. The membrane-bound C4b binds COMPLEMENT C2A, a SERINE PROTEASE, to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
The larger fragment generated from the cleavage of COMPLEMENT C3 by C3 CONVERTASE. It is a constituent of the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb), and COMPLEMENT C5 CONVERTASES in both the classical (C4b2a3b) and the alternative (C3bBb3b) pathway. C3b participates in IMMUNE ADHERENCE REACTION and enhances PHAGOCYTOSIS. It can be inactivated (iC3b) or cleaved by various proteases to yield fragments such as COMPLEMENT C3C; COMPLEMENT C3D; C3e; C3f; and C3g.
Complement activation initiated by the interaction of microbial ANTIGENS with COMPLEMENT C3B. When COMPLEMENT FACTOR B binds to the membrane-bound C3b, COMPLEMENT FACTOR D cleaves it to form alternative C3 CONVERTASE (C3BBB) which, stabilized by COMPLEMENT FACTOR P, is able to cleave multiple COMPLEMENT C3 to form alternative C5 CONVERTASE (C3BBB3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
The smaller fragment formed when complement C4 is cleaved by COMPLEMENT C1S. It is an anaphylatoxin that causes symptoms of immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE) but its activity is weaker than that of COMPLEMENT C3A or COMPLEMENT C5A.
Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).
C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C5 is cleaved by C5 CONVERTASE into COMPLEMENT C5A and COMPLEMENT C5B. The smaller fragment C5a is an ANAPHYLATOXIN and mediator of inflammatory process. The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX.
Enzymes that activate one or more COMPLEMENT PROTEINS in the complement system leading to the formation of the COMPLEMENT MEMBRANE ATTACK COMPLEX, an important response in host defense. They are enzymes in the various COMPLEMENT ACTIVATION pathways.
The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE.
Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors.
The first complement component to act in the activation of CLASSICAL COMPLEMENT PATHWAY. It is a calcium-dependent trimolecular complex made up of three subcomponents: COMPLEMENT C1Q; COMPLEMENT C1R; and COMPLEMENT C1S at 1:2:2 ratios. When the intact C1 binds to at least two antibodies (involving C1q), C1r and C1s are sequentially activated, leading to subsequent steps in the cascade of COMPLEMENT ACTIVATION.
A serine endopeptidase that has specificity for cleavage at ARGININE. It cleaves a variety of prohormones including PRO-OPIOMELANOCORTIN, proluteinizing-hormone-releasing hormone, proenkephalins, prodynorphin, and PROINSULIN.
The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION.
A CALCIUM-dependent endopeptidase that has specificity for cleavage at ARGININE that is near paired basic residues. It cleaves a variety of prohormones including PRO-OPIOMELANOCORTIN; PRORENIN; proenkephalins; prodynorphin; prosomatostatin; and PROINSULIN.
A glycine-rich, heat-labile serum glycoprotein that contains a component of the C3 CONVERTASE ALTERNATE PATHWAY (C3bBb). Bb, a serine protease, is generated when factor B is cleaved by COMPLEMENT FACTOR D into Ba and Bb.
A 77-kDa subcomponent of complement C1, encoded by gene C1S, is a SERINE PROTEASE existing as a proenzyme (homodimer) in the intact complement C1 complex. Upon the binding of COMPLEMENT C1Q to antibodies, the activated COMPLEMENT C1R cleaves C1s into two chains, A (heavy) and B (light, the serine protease), linked by disulfide bonds yielding the active C1s. The activated C1s, in turn, cleaves COMPLEMENT C2 and COMPLEMENT C4 to form C4b2a (CLASSICAL C3 CONVERTASE).
A 105-kDa serum glycoprotein with significant homology to the other late complement components, C7-C9. It is a polypeptide chain cross-linked by 32 disulfide bonds. C6 is the next complement component to bind to the membrane-bound COMPLEMENT C5B in the assembly of MEMBRANE ATTACK COMPLEX. It is encoded by gene C6.
A serine protease that cleaves multiple COMPLEMENT 5 into COMPLEMENT 5A (anaphylatoxin) and COMPLEMENT 5B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It is a complex of CLASSICAL PATHWAY C3 CONVERTASE (C4b2a) with an additional COMPLEMENT C3B, or C4b2a3b.
A 302-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c, and C3dg (955-1303) in the presence COMPLEMENT FACTOR H. Serum proteases further degrade C3dg into C3d (1002-1303) and C3g (955-1001).
A 206-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c (749-954), and C3dg (955-1303) in the presence COMPLEMENT FACTOR H.
Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.
A 63-kDa serum glycoprotein encoded by gene C9. Monomeric C9 (mC9) binds the C5b-8 complex to form C5b-9 which catalyzes the polymerization of C9 forming C5b-p9 (MEMBRANE ATTACK COMPLEX) and transmembrane channels leading to lysis of the target cell. Patients with C9 deficiency suffer from recurrent bacterial infections.
A 80-kDa subcomponent of complement C1, existing as a SERINE PROTEASE proenzyme in the intact complement C1 complex. When COMPLEMENT C1Q is bound to antibodies, the changed tertiary structure causes autolytic activation of complement C1r which is cleaved into two chains, A (heavy) and B (light, the serine protease), connected by disulfide bonds. The activated C1r serine protease, in turn, activates COMPLEMENT C1S proenzyme by cleaving the Arg426-Ile427 bond. No fragment is released when either C1r or C1s is cleaved.
A serine protease that cleaves multiple COMPLEMENT 3 into COMPLEMENT 3A (anaphylatoxin) and COMPLEMENT 3B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It is a complex of COMPLEMENT 4B and COMPLEMENT 2A (C4b2a).
A serine endopeptidase found primarily in the EXTRACELLULAR MATRIX. It has specificity for cleavage of a variety of substrates including PRORENIN, pro-membrane type-1 matrix metalloproteinase, and NEURAL CELL ADHESION MOLECULE L1.
A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the "membrane attack complex" or MAC.
Proteolytic enzymes that are involved in the conversion of protein precursors such as peptide prohormones into PEPTIDE HORMONES. Some are ENDOPEPTIDASES, some are EXOPEPTIDASES.
A 53-kDa protein that is a positive regulator of the alternate pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It stabilizes the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) and protects it from rapid inactivation, thus facilitating the cascade of COMPLEMENT ACTIVATION and the formation of MEMBRANE ATTACK COMPLEX. Individuals with mutation in the PFC gene exhibit properdin deficiency and have a high susceptibility to infections.
The COOH-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S. It is a SERINE PROTEASE. C2a combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
A serum protein which is important in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. This enzyme cleaves the COMPLEMENT C3B-bound COMPLEMENT FACTOR B to form C3bBb which is ALTERNATIVE PATHWAY C3 CONVERTASE.
A 93-kDa serum glycoprotein encoded by C7 gene. It is a polypeptide chain with 28 disulfide bridges. In the formation of MEMBRANE ATTACK COMPLEX; C7 is the next component to bind the C5b-6 complex forming a trimolecular complex C5b-7 which is lipophilic, resembles an integral membrane protein, and serves as an anchor for the late complement components, C8 and C9.
The N-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S.
A serine protease that is the complex of COMPLEMENT C3B and COMPLEMENT FACTOR BB. It cleaves multiple COMPLEMENT C3 into COMPLEMENT C3A (anaphylatoxin) and COMPLEMENT C3B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY.
The larger fragment generated from the cleavage of C5 by C5 CONVERTASE that yields COMPLEMENT C5A and C5b (beta chain + alpha' chain, the residual alpha chain, bound by disulfide bond). C5b remains bound to the membrane and initiates the spontaneous assembly of the late complement components to form C5b-8-poly-C9, the MEMBRANE ATTACK COMPLEX.
Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.
An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).
A serum protein that regulates the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE (C4bC2a).
Molecular sites on or in some B-lymphocytes and macrophages that recognize and combine with COMPLEMENT C3B. The primary structure of these receptors reveal that they contain transmembrane and cytoplasmic domains, with their extracellular portion composed entirely of thirty short consensus repeats each having 60 to 70 amino acids.
A screening assay for circulating COMPLEMENT PROTEINS. Diluted SERUM samples are added to antibody-coated ERYTHROCYTES and the percentage of cell lysis is measured. The values are expressed by the so called CH50, in HEMOLYTIC COMPLEMENT units per milliliter, which is the dilution of serum required to lyse 50 percent of the erythrocytes in the assay.
Endogenous proteins that inhibit or inactivate COMPLEMENT C3B. They include COMPLEMENT FACTOR H and COMPLEMENT FACTOR I (C3b/C4b inactivator). They cleave or promote the cleavage of C3b into inactive fragments, and thus are important in the down-regulation of COMPLEMENT ACTIVATION and its cytolytic sequence.
The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.
A plasma serine proteinase that cleaves the alpha-chains of C3b and C4b in the presence of the cofactors COMPLEMENT FACTOR H and C4-binding protein, respectively. It is a 66-kDa glycoprotein that converts C3b to inactivated C3b (iC3b) followed by the release of two fragments, C3c (150-kDa) and C3dg (41-kDa). It was formerly called KAF, C3bINF, or enzyme 3b inactivator.
An IgG autoantibody against the ALTERNATIVE PATHWAY C3 CONVERTASE, found in serum of patients with MESANGIOCAPILLARY GLOMERULONEPHRITIS. The binding of this autoantibody to C3bBb stabilizes the enzyme thus reduces the actions of C3b inactivators (COMPLEMENT FACTOR H; COMPLEMENT FACTOR I). This abnormally stabilized enzyme induces a continuous COMPLEMENT ACTIVATION and generation of C3b thereby promoting the assembly of MEMBRANE ATTACK COMPLEX and cytolysis.
Important enzymes in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.
A family of SERINE ENDOPEPTIDASES isolated from Bacillus subtilis. EC 3.4.21.-
A proprotein convertase with specificity for the proproteins of PROALBUMIN; COMPLEMENT 3C; and VON WILLEBRAND FACTOR. It has specificity for cleavage near paired ARGININE residues that are separated by two amino acids.
Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.
GPI-linked membrane proteins broadly distributed among hematopoietic and non-hematopoietic cells. CD55 prevents the assembly of C3 CONVERTASE or accelerates the disassembly of preformed convertase, thus blocking the formation of the membrane attack complex.
A 150-kDa serum glycoprotein composed of three subunits with each encoded by a different gene (C8A; C8B; and C8G). This heterotrimer contains a disulfide-linked C8alpha-C8gamma heterodimer and a noncovalently associated C8beta chain. C8 is the next component to bind the C5-7 complex forming C5b-8 that binds COMPLEMENT C9 and acts as a catalyst in the polymerization of C9.
An endogenous 105-kDa plasma glycoprotein produced primarily by the LIVER and MONOCYTES. It inhibits a broad spectrum of proteases, including the COMPLEMENT C1R and the COMPLEMENT C1S proteases of the CLASSICAL COMPLEMENT PATHWAY, and the MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. C1-INH-deficient individuals suffer from HEREDITARY ANGIOEDEMA TYPES I AND II.
Proteins that bind to particles and cells to increase susceptibility to PHAGOCYTOSIS, especially ANTIBODIES bound to EPITOPES that attach to FC RECEPTORS. COMPLEMENT C3B may also participate.
The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.
Complement activation triggered by the interaction of microbial POLYSACCHARIDES with serum MANNOSE-BINDING LECTIN resulting in the activation of MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. As in the classical pathway, MASPs cleave COMPLEMENT C4 and COMPLEMENT C2 to form C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.
The natural bactericidal property of BLOOD due to normally occurring antibacterial substances such as beta lysin, leukin, etc. This activity needs to be distinguished from the bactericidal activity contained in a patient's serum as a result of antimicrobial therapy, which is measured by a SERUM BACTERICIDAL TEST.
An acidic protein found in the NEUROENDOCRINE SYSTEM that functions as a molecular chaperone for PROPROTEIN CONVERTASE 2.
Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.
Molecular sites on or in B-lymphocytes, follicular dendritic cells, lymphoid cells, and epithelial cells that recognize and combine with COMPLEMENT C3D. Human complement receptor 2 (CR2) serves as a receptor for both C3dg and the gp350/220 glycoprotein of HERPESVIRUS 4, HUMAN, and binds the monoclonal antibody OKB7, which blocks binding of both ligands to the receptor.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
Small glycoproteins found on both hematopoietic and non-hematopoietic cells. CD59 restricts the cytolytic activity of homologous complement by binding to C8 and C9 and blocking the assembly of the membrane attack complex. (From Barclay et al., The Leukocyte Antigen FactsBook, 1993, p234)
A ubiquitously expressed complement receptor that binds COMPLEMENT C3B and COMPLEMENT C4B and serves as a cofactor for their inactivation. CD46 also interacts with a wide variety of pathogens and mediates immune response.
Serum peptides derived from certain cleaved COMPLEMENT PROTEINS during COMPLEMENT ACTIVATION. They induce smooth MUSCLE CONTRACTION; mast cell HISTAMINE RELEASE; PLATELET AGGREGATION; and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from the strongest to the weakest is C5a, C3a, C4a, and C5a des-arginine.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A class of C-type lectins that target the carbohydrate structures found on invading pathogens. Binding of collectins to microorganisms results in their agglutination and enhanced clearance. Collectins form trimers that may assemble into larger oligomers. Each collectin polypeptide chain consists of four regions: a relatively short N-terminal region, a collagen-like region, an alpha-helical coiled-coil region, and carbohydrate-binding region.
A specific mannose-binding member of the collectin family of lectins. It binds to carbohydrate groups on invading pathogens and plays a key role in the MANNOSE-BINDING LECTIN COMPLEMENT PATHWAY.
The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.
A ZINC-containing exopeptidase primarily found in SECRETORY VESICLES of endocrine and neuroendocrine cells. It catalyzes the cleavage of C-terminal ARGININE or LYSINE residues from polypeptides and is active in processing precursors of PEPTIDE HORMONES and other bioactive peptides.
Venoms from snakes of the genus Naja (family Elapidae). They contain many specific proteins that have cytotoxic, hemolytic, neurotoxic, and other properties. Like other elapid venoms, they are rich in enzymes. They include cobramines and cobralysins.
Serum serine proteases which participate in COMPLEMENT ACTIVATION. They are activated when complexed with the MANNOSE-BINDING LECTIN, therefore also known as Mannose-binding protein-Associated Serine Proteases (MASPs). They cleave COMPLEMENT C4 and COMPLEMENT C2 to form C4b2a, the CLASSICAL PATHWAY C3 CONVERTASE.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
Abnormal immunoglobulins, especially IGG or IGM, that precipitate spontaneously when SERUM is cooled below 37 degrees Celsius. It is characteristic of CRYOGLOBULINEMIA.
A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
Polysaccharides consisting of mannose units.
Proteins prepared by recombinant DNA technology.
Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
A serine protease that cleaves multiple COMPLEMENT C5 into COMPLEMENT C5A (anaphylatoxin) and COMPLEMENT C5B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. It is the complex of ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) with an additional COMPLEMENT C3B, or C3bBb3b.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.
Antibodies produced by a single clone of cells.
The rate dynamics in chemical or physical systems.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
An adrenal microsomal cytochrome P450 enzyme that catalyzes the 21-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP21 gene, converts progesterones to precursors of adrenal steroid hormones (CORTICOSTERONE; HYDROCORTISONE). Defects in CYP21 cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL).
Established cell cultures that have the potential to propagate indefinitely.
A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.
Important enzymes in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.
Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
A 19-kDa cationic peptide found in EOSINOPHIL granules. Eosinophil-derived neurotoxin is a RIBONUCLEASE and may play a role as an endogenous antiviral agent.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Transport proteins that carry specific substances in the blood or across cell membranes.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
Proteins that share the common characteristic of binding to carbohydrates. Some ANTIBODIES and carbohydrate-metabolizing proteins (ENZYMES) also bind to carbohydrates, however they are not considered lectins. PLANT LECTINS are carbohydrate-binding proteins that have been primarily identified by their hemagglutinating activity (HEMAGGLUTININS). However, a variety of lectins occur in animal species where they serve diverse array of functions through specific carbohydrate recognition.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
Physiologically inactive substances that can be converted to active enzymes.
A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.
Hormones secreted by the PITUITARY GLAND including those from the anterior lobe (adenohypophysis), the posterior lobe (neurohypophysis), and the ill-defined intermediate lobe. Structurally, they include small peptides, proteins, and glycoproteins. They are under the regulation of neural signals (NEUROTRANSMITTERS) or neuroendocrine signals (HYPOTHALAMIC HORMONES) from the hypothalamus as well as feedback from their targets such as ADRENAL CORTEX HORMONES; ANDROGENS; ESTROGENS.
A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.
The sum of the weight of all the atoms in a molecule.
The common precursor polypeptide of pancreatic GLUCAGON and intestinal GLUCAGON-LIKE PEPTIDES. Proglucagon is the 158-amino acid segment of preproglucagon without the N-terminal signal sequence. Proglucagon is expressed in the PANCREAS; INTESTINES; and the CENTRAL NERVOUS SYSTEM. Posttranslational processing of proglucagon is tissue-specific yielding numerous bioactive peptides.
A 66-kDa peroxidase found in EOSINOPHIL granules. Eosinophil peroxidase is a cationic protein with a pI of 10.8 and is comprised of a heavy chain subunit and a light chain subunit. It possesses cytotoxic activity towards BACTERIA and other organisms, which is attributed to its peroxidase activity.
A 30-kDa protein synthesized primarily in the ANTERIOR PITUITARY GLAND and the HYPOTHALAMUS. It is also found in the skin and other peripheral tissues. Depending on species and tissues, POMC is cleaved by PROHORMONE CONVERTASES yielding various active peptides including ACTH; BETA-LIPOTROPIN; ENDORPHINS; MELANOCYTE-STIMULATING HORMONES; and others (GAMMA-LPH; CORTICOTROPIN-LIKE INTERMEDIATE LOBE PEPTIDE; N-terminal peptide of POMC or NPP).
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
Chronic glomerulonephritis characterized histologically by proliferation of MESANGIAL CELLS, increase in the MESANGIAL EXTRACELLULAR MATRIX, and a thickening of the glomerular capillary walls. This may appear as a primary disorder or secondary to other diseases including infections and autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Various subtypes are classified by their abnormal ultrastructures and immune deposits. Hypocomplementemia is a characteristic feature of all types of MPGN.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A gram-positive organism found in the upper respiratory tract, inflammatory exudates, and various body fluids of normal and/or diseased humans and, rarely, domestic animals.
Proteins isolated from the outer membrane of Gram-negative bacteria.
A derivative of complement C5a, generated when the carboxy-terminal ARGININE is removed by CARBOXYPEPTIDASE B present in normal human serum. C5a des-Arg shows complete loss of spasmogenic activity though it retains some chemotactic ability (CHEMOATTRACTANTS).
The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.
A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.
An adhesion-promoting leukocyte surface membrane heterodimer. The alpha subunit consists of the CD11b ANTIGEN and the beta subunit the CD18 ANTIGEN. The antigen, which is an integrin, functions both as a receptor for complement 3 and in cell-cell and cell-substrate adhesive interactions.
ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.
Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.
A plasma protein that circulates in increased amounts during inflammation and after tissue damage.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.
Proteins found in any species of bacterium.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.
The clear portion of BLOOD that is left after BLOOD COAGULATION to remove BLOOD CELLS and clotting proteins.
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
A 69-amino acid peptide derived from the N-terminal of PROGLUCAGON. It is mainly produced by the INTESTINAL L CELLS. Further processing of glicentin yield a 30-amino acid N-terminal peptide (glicentin-related polypeptide) and a 37-amino acid peptide OXYNTOMODULIN. Both glicentin and oxyntomodulin can reduce digestive secretions and delay gastric emptying.
Substances elaborated by bacteria that have antigenic activity.
Enzymes that act at a free C-terminus of a polypeptide to liberate a single amino acid residue.
A genus of trematode flukes belonging to the family Schistosomatidae. There are over a dozen species. These parasites are found in man and other mammals. Snails are the intermediate hosts.
A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.
A serine endopeptidase isolated from Bacillus subtilis. It hydrolyzes proteins with broad specificity for peptide bonds, and a preference for a large uncharged residue in P1. It also hydrolyzes peptide amides. (From Enzyme Nomenclature, 1992) EC 3.4.21.62.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
Thickening of the walls of small ARTERIES or ARTERIOLES due to cell proliferation or HYALINE deposition.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking.
A condition characterized by the recurrence of HEMOGLOBINURIA caused by intravascular HEMOLYSIS. In cases occurring upon cold exposure (paroxysmal cold hemoglobinuria), usually after infections, there is a circulating antibody which is also a cold hemolysin. In cases occurring during or after sleep (paroxysmal nocturnal hemoglobinuria), the clonal hematopoietic stem cells exhibit a global deficiency of cell membrane proteins.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Elements of limited time intervals, contributing to particular results or situations.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
A family of membrane-anchored glycoproteins that contain a disintegrin and metalloprotease domain. They are responsible for the proteolytic cleavage of many transmembrane proteins and the release of their extracellular domain.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Glycoproteins found on the membrane or surface of cells.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A 37-amino acid peptide derived from the C-terminal of GLICENTIN. It is mainly produced by the INTESTINAL L CELLS. Oxyntomodulin can reduce digestive secretions, delay gastric emptying, and reduced food intake.
Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.
Plasma glycoproteins that form a stable complex with hemoglobin to aid the recycling of heme iron. They are encoded in man by a gene on the short arm of chromosome 16.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
A di-isopropyl-fluorophosphate which is an irreversible cholinesterase inhibitor used to investigate the NERVOUS SYSTEM.
The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.
The process of cleaving a chemical compound by the addition of a molecule of water.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).
Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
Glomerulonephritis associated with autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Lupus nephritis is histologically classified into 6 classes: class I - normal glomeruli, class II - pure mesangial alterations, class III - focal segmental glomerulonephritis, class IV - diffuse glomerulonephritis, class V - diffuse membranous glomerulonephritis, and class VI - advanced sclerosing glomerulonephritis (The World Health Organization classification 1982).

Separation of decay-accelerating and cofactor functional activities of Kaposi's sarcoma-associated herpesvirus complement control protein using monoclonal antibodies. (1/3)

Complement is an essential part of the innate immune system, which clears pathogens without requirement for previous exposure, although it also greatly enhances the efficacy and response of the cellular and humoral immune systems. Kaposi's sarcoma-associated herpesvirus (KSHV) is the most recently identified human herpesvirus and the likely aetiological agent of Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease. We previously reported that the KSHV complement control protein (KCP) was expressed on infected cells and virions, and could inhibit complement through decay-accelerating activity (DAA) of the classical C3 convertase and cofactor activity (CFA) for factor I (FI)-mediated degradation of C4b and C3b, as well as acting as an attachment factor for binding to heparan sulphate on permissive cells. Here, we determined the ability of a panel of monoclonal anti-KCP antibodies to block KCP functions relative to their recognized epitopes, as determined through binding to recombinant KCP containing large (entire domain) or small (2-3 amino acid residue) alterations. One antibody recognizing complement control protein (CCP) domain 1 blocked heparin binding, DAA and C4b CFA, but was poor at blocking C3b CFA, while a second antibody recognizing CCP4 blocked C3b CFA and 80% DAA, but not C4b CFA or heparan sulphate binding. Two antibodies recognizing CCP2 and CCP3 were capable of blocking C3b and C4b CFA and heparan sulphate binding, but only one could inhibit DAA. These results show that, while KCP is a multifunctional protein, these activities do not completely overlap and can be isolated through incubation with monoclonal antibodies.  (+info)

Autoantibody stabilization of the classical pathway C3 convertase leading to C3 deficiency and Neisserial sepsis: C4 nephritic factor revisited. (2/3)

 (+info)

Sushi domain-containing protein 4 (SUSD4) inhibits complement by disrupting the formation of the classical C3 convertase. (3/3)

 (+info)

Acts as complement inhibitor by disrupting the formation of the classical C3 convertase. Isoform 3 inhibits the classical complement pathway, while membrane-bound isoform 1 inhibits deposition of C3b via both the classical and alternative complement pathways.
Product Name: PrEST Antigen SUSD4Synonym: FLJ10052Product Type: ChemicalCAS NO: 52-51-7Wee1 inhibitorsAssay: |80% (SDS-PAGE)Concentration:
Human SUSD3 full-length ORF ( NP_659443.1, 1 a.a. - 255 a.a.) recombinant protein with GST-tag at N-terminal. (H00203328-P01) - Products - Abnova
Routinely used therapies are not adequate to treat the heterogeneity of breast cancer, and consequently, more therapeutic targets are desperately needed. To identify novel targets, we generated a breast cancer cDNA library enriched for genes that encode membrane and secreted proteins. From this library we identified SUSD2 (Sushi Domain Containing 2), which encodes an 822-amino acid protein containing a transmembrane domain and functional domains inherent to adhesion molecules. Previous studies describe the mouse homolog, Susd2, but there are no studies on the human gene associated with breast cancer. Immunohistochemical analysis of human breast tissues showed weak or no expression of SUSD2 in normal epithelial cells, with the endothelial lining of vessels staining positive for SUSD2. However, staining was observed in pathologic breast lesions and in lobular and ductal carcinomas. SUSD2 interacts with galectin-1 (Gal-1), a 14-kDa secreted protein that is synthesized by carcinoma cells and ...
STOCKTON - A seat is empty on the Stockton Unified School District governing board as Ed Garcia, who had served as a trustee for seven years, resigned.
Use Bio-Rads PrimePCR assays, controls, templates for your target gene. Every primer pair is optimized, experimentally validated, and performance guaranteed.
Use Bio-Rads PrimePCR assays, controls, templates for your target gene. Every primer pair is optimized, experimentally validated, and performance guaranteed.
With two holes open, the filtering effect of the downstream holes is clear at frequencies above about 1.5 kHz. Compare this spectrum with more regular impedance spectrum for D4 on the classical instrument with a D foot. The regular, harmonically spaced minima in the latter spectrum allow greater power in the higher harmonics, and thus a brighter tone for this note.. ...
Located in Aventura, Sushi Sakes sushi rolls are bursting with flavor and color.Diners will appreciate the quick and easy parking options located near this dining establishment.If you have a hankering for some unique sushi dishes, make your way over to Sushi Sake.
Its called Blowfish - Sushi to Die For; and what an experience it is. Blowfish Sushi is Hipster Sushi In The Heart of Parnell and it is now open for lunch and dinner in the heart of Parnell. Blowfish Sushi offers an exciting and unconventional environment ...
There are five basic kinds of sushi: maki, nigiri, temaki, chirashi, and inari sushi. Though most people think of sushi as simply...
Sushi domain containing protein 4 (SUSD4) is a newly discovered, but poorly characterized transmembrane protein. The structure of SUSD4 shows a high degree of homology among species, including 91% identity between mouse and man. SUSD4 is broadly expressed in human and mouse tissues including pancreatic islets. Therefore, in this study, we investigate the possible role of SUSD4 in the major function of pancreatic islets, which is insulin secretion. We found that SUSD4 KO mice displayed significantly impaired blood glucose clearance, which was aggravated with age and by a high fat diet. This defect was not due to increased insulin resistance of SUSD4 KO mice. Isolated islets from SUSD4 KO mice secreted less insulin upon stimulation with glucose and high KCl. No developmental malformation or morphological defect of pancreas or islets in SUSD4 KO mice was detected via Optical Projection Tomography (OPT), which allows the three-dimensional imaging of the spatial and quantitative distribution of the ...
The heart of sushi is the rice. Without rice there would not be sushi. The very word sushi means vinegared rice. There are a number of important factors to successful, delicious sushi rice. First, you must use white, short or medium grain rice which will give you a soft, sticky consistency. Secondly, you must use a rice cooker. An electric rice cooker is essential for perfect, no fail rice for sushi.. ...
Although sushi is the common food, most people have doubt that is sushi healthy or not? 100% sushi is the diet food and has low caloric value and high
How do you roll? This extensive list of sushi rolls contains the most popular Westernized varieties of the Japanese delight (i.e. Texas rolls are n...
Sushi is more popular than ever before but eating it has become the new Russian roulette in terms of safety. One mans love of sashimi nearly killed him after
Make the perfect sushi roll every time by yourself whenever you use the Yomo Sushi maker. Its a simple sushi rolling system and roll cutter, the purpose of which is to give you the power of making perfect Sushis at home. The one piece set will not only help you in getting to that ideal roll but also gives you the correct side piece with the roll cutter. The patented and mat replace the traditional bamboo and messy and inconsistent handmade rolls ...
The expression values of Her2, PR, and ER and subtype designation are correlated with the metagenes of BCAM and therefore are indirectly taken into account. They obviously provide vital information and improved understanding of breast cancer biology, which has led to effective treatments. However, our results suggest that an optimum breast cancer biomarker product does not need to include them.. Many early versions of microarray platforms, notably the popular Affymetrix U133A, do not contain probes for FGD3 and SUSD3, which may provide some explanation as to why these genes were not found earlier as highly prognostic in breast cancer. The two genes are genomically adjacent to each other and are correlated with ESR1 and PGR. The simultaneous silencing of FGD3 and SUSD3 is strongly associated (6) with poor prognosis. Furthermore, a recent study (21) identified SUSD3 as the single most predictive gene (more than ESR1) of response to aromatase inhibitor therapy. On the basis of the above facts, we ...
So what do you do if you run out of nori in the middle of making sushi? Well, after the initial oh crud moment, you find a way to replace it. Lucky for me, I have a TON of spring roll wrappers laying around, which turn out to be the perfect replacement for nori. Not only are they sturdy enough to roll sushi in without falling apart, they are also fairly bland, so theyre great for people who dont like the taste of nori in the first place.. Since the name sushi refers to the seasoned rice that is used rather than the way the roll is made, these rolls that are reminiscent of spring rolls can still be considered sushi. But if you are making them at home, dont feel like you have to eat them just like sushi. Youre free to skip slicing them into several pieces, and instead eat them with your hands and dip them into a sauce just like you might a spring roll.. Oh, and before I give you the recipe, I must say something about the sauce. This sauce is amazing. Sure the combination sounds a little ...
Once you have mastered plain rice, turning it into sushi rice (shari) just requires a few more steps. Sushi rice (called shari by sushi chefs) is rice that is flavored with dashi, rice vinegar, and salt.. Substitute cooled dashi stock for the water. Cook as per the above instructions.. You will need a large bowl or plate for the next step, preferably a wooden one made for this purpose called a hangiri. You can buy a hangiri at any Japanese kitchen equipment store, and even from Amazon. The advantage of using a wooden hangiri is that the untreated wood absorbs excess moisture from the rice. You can also use a large serving plate or a bowl, though that wont have the moisture-absorbing quality.. You also need a sturdy rice paddle or spatula. rice cookers come with a rice paddle.. Take 1/4 cup of bottled or homemade sushi vinegar (sushi-zu or awase-zu, see recipe below). Moisten your spatula or paddle with a little of the vinegar. Turn your hot rice out into the bowl or plate, Pour the sushi ...
You can order lots of varieties of Sushi. There are various types of rolls, fishes, vegetables, garnishes, etc. to choose from. You will never be tired of eating Sushi. You will always find something new to taste.. So, if you havent tried Sushi yet, there are many reasons to try it now. Its a unique dish that looks great and tastes good, too! So, dont miss it!. ...
Perfect sushi starts with perfect rice. Heres an easy recipe for Japanese sushi rice. For best results, use starchy short or medium-grain rice.
Book now at Sushi Lounge in Hoboken, NJ. Explore menu, see photos and read 93 reviews: Specialty rolls were very creative but the sushi was not as good as expected. A few rolls had been refrigerated. Others seemed not so fresh. I will pro...
Create some of the most visually appealing and tasty sushi rolls imaginable with this Bamboo Rolling Mat from Kotobuki. This sushi mat allows the user
Many people believed sushi was a nutritious meal and a smart choice for heart health, but a recent study suggests the Japanese food could actually increase the risk of cardiovascular disease.
A small American restaurant chain called Sticky Rice has successfully launched the very first sushi into space on Jan. 1 this year. As...
The Japanese are so evolved, theyve figured out nearly everything to an art. We thought these cute little sushi couldnt probably look any cuter. We were
Pat Pong in Bangkok. The place charges 199 baht (about RM 20) for an all-you-can-eat buffet of shabu shabu (not that kind, the Japanese steamboat) and sushi. The name Shabu shi is a contraction of the words Shabu shabu and Sushi.. ...
Hello Susan! For me it has to be coconut & lime because it just such a summery scent and for us in New Zealand Christmas means long hot days at the beach with family & friends (and kind of reminds me of the coconut oil we used to slather on ourselves years ago - yikes!) We love a warm Christmas - strange concept I know!! Camphor is also a favourite as it reminds me of my grandmothers camphorwood chest that we were never allowed to rummage through (but desperately wanted to) as kids. When she did open it... ahhhh that smell. Also anything floral as everything in my garden is in full bloom - heavenly ...
Biologists and law enforcement are pushing to dismantle these unauthorized weed grow sites found on the states federal and state parks.
Minumnya seperti biasa, ocha yang free...hahahaha. Buat gua, Sushi Tei tetep yang paling enak dibanding restoran sushi lainnya. Btw, sedikit intermezzo. Katanya kalo di Jepang itu hampir semua sushi mentah, ga ada yang mateng. Sushi mateng macam fussion roll itu modifikasi dari barat karena mereka ga suka makanan mentah. Dan katanya lagi, kalo di Jepang, wasabi itu uda ada di dalem sushinya, bukan dicampur ke soyu kayak di Indonesia. Dan lagi, di Jepang, mereka makan sushi tanpa soyu. Kalaupun dengan soyu, paling cuma dicocol dikit, bukan direndem kayak yang biasa nyokap gua makan...hahahaha. ...
BEST SUSHI SANSEI SEAFOOD RESTAURANT AND SUSHI BAR Man do I love me some SANSEI! Just saying SANSEI gets me all hella excited. Apparently you like SANSEI too. I dare you to say SANSEI to a hungry friend around dinner time...what do you think is gonna happen? Countless plates of cajun seared walu, maki-maki roll, panko crusted ahi and plenty of ono sushi is whats gonna … [Read more...] about MauiTime Best of Maui 2018: Best Sushi on Maui: Sansei Seafood Restaurant and Sushi Bar ...
Being Tom Hanks á la Castaway has one major drawback: being stuck on an island with only a volleyball to call friend. But it also has one redeeming benefit: fresh, healthy sushi! Since we lost the deed to our ocean-front office space in a heated game of laser tag, our access to fresh fish has been somewhat limited, meaning weve had to resort to Westernized versions of sushi for our fish fix. Unfortunately most of these rolls make the dangerfood list (dun dun duuun). ...
Umi Sushi, Jacksonville: See 71 unbiased reviews of Umi Sushi, rated 4.5 of 5 on TripAdvisor and ranked #11 of 26 restaurants in Jacksonville.
I had the opportunity to try out their Asian Fusion Restaurant named Bashi.. This resturant is a must try not only because of its gorgous views, but also because of their great happy hour deal! During their happy hour which is daily between 4:00-6:00PM they offer half off sushi rolls and special prices sake and cocktails. I found the sushi to be of great quality and fresh.. ...
The next time you have a serious craving for sushi — and a lunch date with your vegetarian buddy — consider Manpuku. This smallish sushi...
When eaten properly, sushi is very good for you. Though some have fears about eating raw fish, properly prepared sushi is actually...
Moosoo Sushi has more than 70 kinds of fusion sushi rolls and dishes. Our reccipes and culinary methods follow Japanese traditions fused with refreshing, new and exciting ideas.We are committed to quality and freshness.
I will use this thread to document the whole making of my movie: SLICE OF LIFE. So, apart from Sushi bar there will be many other models, props, tests, videos and stuff. Hope youll like it! ------------------------------------------------------ Hi! Im sure most of you are familiar with the Sushi bar building. It was just one of randomly put together buildings and used in most of the SFX shots in the movie called Blade Runner. I was fascinated with the shape and look of that building
Update: Ive updated this post substantially in these two articles, 10 years later: How to cook great Japanese style rice, and How to make sushi rice (shari). Please take a look there - youll probably find them a lot clearer. Ive learned a lot myself in 10 years! ^_^ This is the first how-to and recipe that I posted on Just Hungry. Properly cooked rice is the foundation of a
I will use this thread to document the whole making of my movie: SLICE OF LIFE. So, apart from Sushi bar there will be many other models, props, tests, videos and stuff. Hope youll like it! ------------------------------------------------------ Hi! Im sure most of you are familiar with the Sushi bar building. It was just one of randomly put together buildings and used in most of the SFX shots in the movie called Blade Runner. I was fascinated with the shape and look of that building
OK, so here are some industry secrets to help you buy sushi grade fish when Kazari can’t help you. That being said, the following can apply to any...
We went out a couple nights ago for the last MNO for me - probably ever. Sad, sad. And they surprised me by bringing a gift - supplies for sushi making no less! They explained that they were concerned that I wouldnt have yummy sushi access after the move ...
fruit sushi - Traditionally, sushi consists of rice, seaweed, vegetables and raw fish, but this fruit sushi is a slightly sweeter take on the Japanese cuisine. C...
There are 367 calories in 1 container, 3 pieces (4.9 oz) of Hissho Sushi Inari Sushi. Youd need to walk 96 minutes to burn 367 calories. Visit CalorieKing to see calorie count and nutrient data for all portion sizes.
There are 494 calories in 1 container, 8 pieces (9.9 oz) of Hissho Sushi The Alaskan Sushi. Youd need to walk 129 minutes to burn 494 calories. Visit CalorieKing to see calorie count and nutrient data for all portion sizes.
We left her house at 6 pm to go pick up some sushi. Seems like an easy enough task! We went to a Thai place where they told us they only had sushi on Thursday nights. So she decided to order a couple of meals and then we would go by and pick up a little bit of sushi from another place. After waiting 30 min and the food STILL wasnt out she decided to call in the sushi order to save some time. 15 min later we finally got our food and were headed to the sushi place. I usually eat at 6:30 or 7:00 and by this time it was 7:00. If you know me, you know I cant go more than 2 to 3 hours without eating! We arrived at the sushi place 30 min after she called it in. It wasnt ready! We waited there another 30 min! Every single Jersey Shore want to be guy must have been at that sushi place. They were like sharks circling their prey. At this time Julie looks at me and says she needs to go by McDonalds to get Austin something. Im about to lose it at this point so I told her to go and I would wait for the ...
Best Sushi in Roslyn, Washington: Find TripAdvisor traveller reviews of Roslyn Sushi restaurants and search by price, location, and more.
Reserve a table at Istana Sushi and Wok Inc, Hoboken on TripAdvisor: See 4 unbiased reviews of Istana Sushi and Wok Inc, rated 4 of 5 on TripAdvisor and ranked #200 of 308 restaurants in Hoboken.
Book now at RA Sushi Bar Restaurant - Tempe in Tempe, explore menu, see photos and read 72 reviews: Really enjoyed the sushi, great variety.
Best Sushi in Kato Daratso, Chania Prefecture: Find TripAdvisor traveller reviews of Kato Daratso Sushi restaurants and search by price, location, and more.
Is Sushi Healthy. There is so much misinformation on this subject so we take the most popular ingredients and weigh both the positive and negative benefits on your health.
The owner of Japanese restaurant chain Genki Sushi Co (9828.T) will buy a one-third stake in bigger rival Sushiro Global Holdings Ltd (3563.T) from private equity firm Permira [PERM.UL], a person with direct knowledge of the deal said.
fr C3 convertase classique * en classical-complement-pathway C3/C5-convertase Immunologia ... C3/C5-convertasa de la via clàssica del complement C3/C5-convertasa de la via clàssica del complement ... ca C3/C5-convertasa de la via clàssica del complement, n f ... es C3/C5-convertasa de la vía clásica del complemento * ... de la via clàssica del complement amb la via alternativa i amb la via de la lectina i que escindeix el factor del complement C3 ...
EC 3.4.21.43: classical-complement-pathway C3/C5 convertase * EC 3.4.21.44: complement component C5 convertase ... EC 3.4.21.46: complement factor D * EC 3.4.21.47: alternative-complement-pathway C3/C5 convertase ...
Isoform 3 inhibits the classical complement pathway, while membrane-bound isoform 1 inhibits deposition of C3b via both the ... Acts as complement inhibitor by disrupting the formation of the classical C3 convertase. ... Acts as complement inhibitor by disrupting the formation of the classical C3 convertase. Isoform 3 inhibits the classical ... "Sushi domain-containing protein 4 (SUSD4) inhibits complement by disrupting the formation of the classical C3 convertase.". ...
The crystal structure of c2a, the catalytic fragment of classical pathway c3 and c5 convertase of human complement.. Krishnan, ... convertases of the classical and lectin pathways of complement activation. Formation of these convertases requires the Mg(2+)- ... convertases of the classical and lectin pathways of complement activation. Formation of these convertases requires the Mg(2+)- ... Complement component C2a, the catalytic fragment of C3- and C5-convertase of human complement. *DOI: 10.2210/pdb2ODP/pdb ...
Anticomplementary activity of Boswellia acids--an inhibitor of C3-convertase of the classical complement pathway. ... Denoting a substance possessing the power to diminish or abolish the action of a complement. ... on the differential anticomplementary effects of dextran sulphate and heparin in the assay for the mouse alternative pathway.. ...
The assembly of C3 convertases (C4b2a and C3bBb) is a prerequisite for complement activation. The convertases catalyze C3b ... The complement system is pivotal in host defense but also contributes to tissue injury in several diseases. ... interfering with additional C3b deposition through the classical, lectin and alternative complement pathways. This led to a ... The assembly of C3 convertases (C4b2a and C3bBb) is a prerequisite for complement activation. The convertases catalyze C3b ...
... the classical, lectin, and alternative pathways. Cleavage of complement C3 by a free floating convertase, thrombin, plasmin or ... Since C3 convertases cleave C3 to produce C3b which can then form an additional C3 convertase through the alternative pathway, ... C3 convertase can be used to refer to the form produced in the alternative pathway (C3bBb) or the classical and lectin pathways ... "Formation of classical C3 convertase during the alternative pathway of human complement activation". Biokhimiia (Moscow, Russia ...
Chicken polyclonal C3 antibody. Validated in ELISA and tested in Mouse, Human. Cited in 6 publication(s). Immunogen ... Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation ... Defects in C3 are the cause of complement component 3 deficiency (C3D) [MIM:120700]. A rare defect of the complement classical ... C3 plays a central role in the activation of the complement system. ...
... autoantibodies targeted at complement components. Stabilise C3 convertase leading to consumption of C3 ... SLE: The classical pathway clears necrotic and apoptotic cells. Failure leads to build up of self antigens especially nuclear ... Formation of antigen-antibody complexes activates which complement pathway? Starts with which protein? ... C4b binds to the pathogen and starts the process forming C3 convertase. ...
... we have prepared human C3/CVF hybrid proteins, in which the C-terminus of the α-... ... To obtain proteins with the complement-depleting activity of Cobra Venom Factor (CVF), but with less immunogenicity, ... The serine protease nature of the C3 and C5 convertases of the classical and alternative complement pathways. Scand J Immunol 5 ... Pangburn, M. K. and Müller-Eberhard, H. J. (1986). The C3 convertase of the alternative pathway of human complement. Enzymic ...
Rabbit recombinant monoclonal C3 antibody [EPR2988] conjugated to Alexa Fluor® 488. Validated in Flow Cyt, ICC/IF and tested in ... Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation ... Defects in C3 are the cause of complement component 3 deficiency (C3D) [MIM:120700]. A rare defect of the complement classical ... Protein - Recombinant Human C3 protein (ab157985) ELISA, WB Primary - Anti-C3 antibody [EPR2988] (Alexa Fluor® 647) (ab196639) ...
These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. ... Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A ... Complement 5 Convertase; Complement C3 Convertases; Complement C5 Convertases; Activator, C3; C3 Convertases, Complement; C3-C5 ... Convertase, C3; Convertase, C3-C5; Convertase, Complement 3; Convertases, Complement C3; Convertases, Complement C3-C5; ...
In the alternative complement pathway, C3 is cleaved by C3bBb, another form of C3-convertase composed of activated forms of C3 ... Its activation is required for both classical and alternative complement activation pathways. People with C3 deficiency are ... "Entrez Gene: C3 complement component 3". Sahu A, Lambris JD (Apr 2001). "Structure and biology of complement protein C3, a ... C3 convertase. C3bBb is deactivated in steps. First, the proteolytic component of the convertase, Bb, is removed by complement ...
... far exceeding the classical examples of diseases associated with complement deficiencies. Finally, we discuss complement as a ... Inadequate complement activation becomes a disease cause, as in atypical hemolytic uremic syndrome, C3 glomerulopathies, and ... In pathology, complement can be a friend or a foe. It acts as a friend in the defense against pathogens, by inducing a direct ... In pathology, complement can be a friend or a foe. It acts as a friend in the defense against pathogens, by inducing ...
... the classical, alternative, and lectin pathways (2). These pathways converge at the complement component 3 (C3) convertase, ... 2A). The C3 convertase, C4bC2a, formed via activation of either the lectin or the classical pathway enables C3 deposition. Sera ... The lectin pathway is required for C3 deposition. (A) Simplified schema of the classical and lectin pathways of complement ... Binding of the central complement protein C3 to wild-type immature thymocytes required the lectin but not the classical pathway ...
C3, into C3a, an anaphylactic and antimicrobial peptide, and opsonin C3b. In the classical and lectin pathways, C3 convertase ... C3 convertase and amplification. C3 convertase cleaves the central component of complement, ... The complement cascade (CC) can be divided into four major phases: early complement activation; C3-convertase activation and ... Early complement activation. Complement is activated through three different pathways. The alternative pathway is spontaneously ...
... enzyme that regulates both classical and alternative pathways of complement activation by inactivating their C3 convertases. ... C3 nephritic factor (C3 NeF) an autoantibody that stabilizes the alternative complement pathway C3 convertase, preventing its ... C3 nephritic factor (C3 NeF) an autoantibody that stabilizes the alternative complement pathway C3 convertase, preventing its ... enzyme that regulates both classical and alternative pathways of complement activation by inactivating their C3 convertases. ...
The three pathways converge to form C3 convertases, multimeric protein complexes with enzymatic activity (10). Cleavage of C3 ... Complement may indirectly enhance antibody production by augmenting T cell help (not shown). Classical pathway-dependent, ... An analog of the human complement-regulatory protein CD35 (CR1; blocks complement activation at the C3 convertase step) has ... Subsequent cleavage and assembly of C4 and then C2 form the C4bC2b C3 convertase. C3 spontaneously binds to H2O, forming C3(H2O ...
... pathways, orthologs, and expression. GeneCards - The Human Gene Compendium ... Complement Component 4 Binding Protein Alpha, including: function, proteins, disorders, ... complement component 4,binding protein alpha,70kDa,regulator of C3 convertase of classical pathway,see [email protected] *C4BPA ... Immune response Lectin induced complement pathway. Immune response Lectin induced complement pathway ...
... sheep erythrocytes by guinea pig serum via possible inhibition of the C3 convertase of the classical complement pathway. ... been reported to demonstrate inhibitory effects on both the classical pathway convertase and the alternative pathway convertase ... 28 Rosmarinic acid was also reported to inhibit C5 convertase in the classical pathway.48,28 ... a new inhibitor of complement C3-convertase with anti- inflammatory activity. Int J Immunopharmacol 1988;10(6):729-737. 3198307 ...
C4b-binding protein (C4bp) participates in the regulation of the C3 convertase of the classical pathway of complement [26]. ... Regulation and deregulation of the fluid-phase classical pathway C3 convertase. Gigli, I., Sorvillo, J., Halbwachs-Mecarelli, L ... Regulation of complement classical pathway by association of C4b-binding protein to the surfaces of SK-OV-3 and Caov-3 ovarian ... C4b-binding protein (C4BP) inhibits all pathways of complement activation, acting as a cofactor to the serine protease factor I ...
... or ficolins and generation of classical pathway C3 convertase via cleavage of C4 and C2 by MBL-associated serine protease 2 ( ... Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2.. Selander B1, Mårtensson U ... Independent of MBL, specific antibodies to CO supported C3 deposition through classical and alternative pathways. MBL-dependent ... Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2 ...
... pathways. The activation pathways converge in the formation of C3 convertase complexes, which lead to the activation of further ... Control of the classical and the MBL pathway of complement activation. Mol. Immunol. 37:803-811. ... Activation of the classical complement pathway by mannose-binding protein in association with a novel C1s-like serine protease ... The activation of the complement system is initiated through three different pathways: the classical, the alternative, and the ...
Complement System Proteins Vaccinia virus Classical Pathway Complement C3 Convertase Classical Complement Pathway ... Regulation of complement activity by vaccinia virus complement-control protein. McKenzie, R., Kotwal, G. J., Moss, B., Hammer, ... Inhibition of the complement cascade by the major secretory protein of vaccinia virus. Kotwal, G. J., Isaacs, S. N., McKenzie, ...
Indeed, it now seems clear that complement first evolved as part of the innate immune system, where it still plays an important ... Although first discovered as an effector arm of the antibody response, complement can also be activated early in infection in ... This activity was said to complement the antibacterial activity of antibody, hence the name. ... Complement was discovered many years ago as a heat-labile component of normal plasma that augments the opsonization of bacteria ...
Uncontrolled activation of the complement system during sepsis and SIRS with in excessive generation of complement activation ... The underlying immune response is highly complex and involves activation of the complement system as a crucial entity of innate ... mechanisms of the inflammatory response in the development of MOF in sepsis and SIRS with particular focus on the complement ... the classical, the alternative, and the lectin pathway [31-33]. All three pathways lead to the assembly of the C3 convertase ...
2. classic pathway. 3. Alternative pathway. - all result in an enzyme cascade in the blood create C3 convertases 3 ... Complement is activated and get obstruction of vessels and ischemia -Destruction of tissue then occurs to donor kidney. ... F I, H related proteins (alternative**, also in lectin and classical) 100 ... C3 convertases influence 3 different pathways. What molecules are effected and what is the end result? ...
... the classical pathway convertase, leading to the activation of C3 convertase and generation of the terminal complement complex ... Complement studies revealed C3 of 68 mg/dL (reference range, 90-180 mg/dL), fourth component of complement (C4) of 19 mg/dL ( ... via the activation of the classical complement pathway in association with bacterial infections such as coagulase negative ... Complement levels revealed C3 of 45 mg/dL, C4 of 18 mg/dL, and CH50 , 13 mg/dL. Blood cultures revealed coagulase negative ...
Complement Proteins offered by Sigma-alderich online.The complement system is a complex cascade involving proteolytic cleavage ... Classical, Alternate and Lectin Pathways. All three pathways merge through at common intersection, complement C3. ... The two activated C1s subunits are then able to catalyze the assembly of the C3 convertase (complement C4b2a) from complements ... The Classical Pathway:. The classical pathway mediates specific antibody responses. The classical pathway is initiated by the ...
... features revealed by our structural studies are probably involved in the assembly of the classical pathway C3/C5 convertases ... Complement component C4 is a central protein in the classical and lectin pathways within the complement system. During ... Complement component C4 is a central protein in the classical and lectin pathways within the complement system. During ... Structural Basis for the Function of Complement Component C4 within the Classical and Lectin Pathways of Complement.. Mortensen ...
  • In the classical pathway, this is by sequential proteolytic activation of proteins within the C1 complex (C1q, C1r, C1s) in response to binding to CRP or immunoglobulin, and in the lectin pathway it is driven by mannose binding lectin and its associated serine proteases (MASPs, particularly MASP2 but also MASP1). (wikipedia.org)
  • We show that these hybrid proteins are able to deplete complement, both in vitro and in vivo. (springer.com)
  • Human C3/CVF hybrid proteins represent a novel class of biologicals as potential therapeutic agents in many diseases where complement is involved in the pathogenesis. (springer.com)
  • Functional characterization of cobra venom factor/cobra C3 hybrid proteins. (springer.com)
  • Human C3/cobra venom factor hybrid proteins with potential therapeutic applications. (springer.com)
  • Human C3/cobra venom factor hybrid proteins for therapeutic complement depletion: in vivo activity and fine mapping of important domains. (springer.com)
  • First, the proteolytic component of the convertase, Bb, is removed by complement regulatory proteins having decay-accelerating factor (DAF) activity. (wikipedia.org)
  • Unfortunately, the lack of coherence in complement proteins nomenclature and the complexity of the enzymatic cascade render complement one of the "most complicated and incomprehensible" parts of immunology and is frequently avoided by students and scientists. (frontiersin.org)
  • In vivo, T cell maturation entails increasing resistance to complement proteins. (jimmunol.org)
  • Recent thymic emigrants that fail postpositive selection maturation are targeted by complement proteins. (jimmunol.org)
  • Complement activation relies on interplay between multiple soluble proteins and receptors via three main mechanisms: the classical, alternative, and lectin pathways ( 2 ). (jimmunol.org)
  • The decreased expression of complement regulatory proteins (CRP) seems to play an important role in RA activity, and is associated with worsening of the clinical symptoms. (scielo.br)
  • rheumatoid arthritis, complement system proteins, complement activation. (scielo.br)
  • The complement system (CS) is composed of receptors and regulators bound to the cell membrane and different plasma proteins that interact with cells and mediators of the immune system ( Figure 1 ). (scielo.br)
  • Reconstitution of undiluted serum with C1q (70 mg/l, not shown) or D (1 mg/l) together with P (25 mg/l) did not promote C3 deposition, showing that the CO antigen did not activate complement in the absence of recognition proteins. (nih.gov)
  • One component of the innate immune system is the complement system, encompassing more than 30 different recognition, effector, and control proteins. (asm.org)
  • The structural and functional properties of MBL, L-ficolin, and H-ficolin appear very similar, suggesting that the three proteins may serve similar biological functions through activation of the complement system upon binding to microorganisms. (asm.org)
  • The complement system is made up of a large number of distinct plasma proteins that react with one another to opsonize pathogens and induce a series of inflammatory responses that help to fight infection. (nih.gov)
  • A number of complement proteins are proteases that are themselves activated by proteolytic cleavage. (nih.gov)
  • In this way, the activation of a small number of complement proteins at the start of the pathway is hugely amplified by each successive enzymatic reaction, resulting in the rapid generation of a disproportionately large complement response. (nih.gov)
  • First, it generates large numbers of activated complement proteins that bind covalently to pathogens, opsonizing them for engulfment by phagocytes bearing receptors for complement. (nih.gov)
  • Second, the small fragments of some complement proteins act as chemoattractants to recruit more phagocytes to the site of complement activation, and also to activate these phagocytes. (nih.gov)
  • Furthermore, using a new classical pathway convertase model, we show that these C3b-binding proteins not only block AP C3/C5 convertases but also inhibit formation of a functional classical pathway C5 convertase under well-defined conditions. (frontiersin.org)
  • The human complement system comprises a family of proteins that are essential to the human immune response against infections ( 1 ). (frontiersin.org)
  • Complement is a system of plasma proteins that is activated by the presence of pathogens. (wikipathways.org)
  • The Classical pathway of activation of the complement system is a group of blood proteins that mediate the specific antibody response. (wikipathways.org)
  • The complement system is a network of more than 50 plasma proteins and receptors, which have the role of mediating innate and adaptive host defence mechanisms, whereas they also participate in various (patho)physiological processes. (els.net)
  • The primary functions mediated by complement proteins include phagocytosis of foreign elements (bacteria, viruses, particles etc .), cell lysis, inflammation, solubilisation of immune complexes, apoptotic cell clearance and enhancement of humoral immune responses. (els.net)
  • Complement is a multiprotein network of plasma proteins and cell surface receptors. (els.net)
  • Kirjavainen V, Jarva H, Biedzka Sarek M, Blom A, Skurnik M, Meri S. Yersinia enterocolitica serum resistance proteins YadA and ail bind the complement regulator C4b-binding protein. (labome.org)
  • Human complement receptor 1 (CR1, CD35) is a single chain transmembrane glycoprotein of molecular weight 160 kd to 250 kd (depending on allotype) and is a member of the regulators of complement activators (RCA) family of proteins that prevent excessive complement activation by inhibiting key enzymes, C3 and C5 convertases of the 3 complement pathways, namely the classical, alternative, and lectin. (bloodjournal.org)
  • Methods and Results- Human coronary artery or human saphenous vein ECs were incubated with CRP (0 to 100 μg/mL, 0 to 72 hours), and the expression of the complement-inhibitory proteins decay-accelerating factor (DAF), membrane cofactor protein (CD46), and CD59 were measured by flow cytometry. (ahajournals.org)
  • The increased expression of complement-inhibitory proteins was functionally effective, resulting in significant reduction of complement-mediated lysis of antibody-coated human saphenous vein ECs. (ahajournals.org)
  • The complement system is a complex cascade of enzymes and regulatory proteins that normally participate in host defenses against microorganisms via opsonization, chemoattraction of leukocytes, cell lysis, and cell activation. (ahajournals.org)
  • Because complement-inhibitory proteins protect the endothelium from complement-mediated injury and CRP is proatherogenic, in part because of its ability to activate complement, we hypothesized that the detrimental effect of CRP may involve the downregulation of these protective proteins. (ahajournals.org)
  • This family contains two mammalian proteins, complement C2 and complement factor B, which, respectively, have analogous roles in the classical and alternative pathways of complement activation. (ebi.ac.uk)
  • These proteins are composed of three regions, an N-terminal three-module complement control protein domain, a von Willebrand factor A domain, and a C-terminal serine protease domain. (ebi.ac.uk)
  • Briefly, they are activated by cleavage and function as the serine protease components of the C3/C5 convertases, which play similar roles in these pathways although composed of different proteins. (ebi.ac.uk)
  • The complement system consists of a number of small proteins found in the blood, in general synthesized by the liver, and normally circulating as inactive precursors (pro-proteins). (technologynetworks.com)
  • Over 30 proteins and protein fragments make up the complement system, including serum proteins, serosal proteins, and cell membrane receptors. (technologynetworks.com)
  • Most of the proteins and glycoproteins that constitute the complement system are synthesized by hepatocytes. (technologynetworks.com)
  • X-ray and neutron-scattering techniques characterize proteins in solution and complement high-resolution structural studies. (royalsocietypublishing.org)
  • We also discuss the applications to the large multi-domain proteins of the complement system, most notably its major regulator factor H, which is important in age-related macular degeneration and renal diseases. (royalsocietypublishing.org)
  • In recent years, a greater range of proteins have been successfully studied by scattering, including antibodies of adaptive immunity and the complement proteins of innate immunity. (royalsocietypublishing.org)
  • The complement system is composed of about 20 different proteins released into the blood after production in the liver. (epomedicine.com)
  • This pathway consists of proteins known by the term "Factors" like Factor B, Factor D. (epomedicine.com)
  • The classical pathway consists of 4 proteins C1, C2, C3 and C4. (epomedicine.com)
  • The lectin pathway consists of C2, C3, C4 and some calcium-dependent lectin family proteins which are homologous to C1 component. (epomedicine.com)
  • When MBL grabs its target (mannose on the surface of a bacterium, for example), the MASP protein functions like a convertase to clip C3 complement proteins to make C3b. (epomedicine.com)
  • The complement system consists of thirty five interacting plasma and membrane associated proteins which contribute to host-defense and initiate and amplify inflammation, even in the preimmune state where specific antibodies and lymphocytes are not available. (genetex.com)
  • In addition to the complement components themselves, this system also contains several soluble factors that prevent spontaneous complement activation from occurring in solution, as well as, several regulatory membrane associated proteins that protect host cells from accidental complement attack. (genetex.com)
  • The gene encoding FH is localized on the long arm of chromosome 1 at 1q32, a locus called RCA (regulators of complement activation) ( 8,9 ⇓ ), which contains genes encoding different regulatory proteins of complement activation ( 10 ). (asnjournals.org)
  • The complement system, which consists of more than 30 soluble and cell surface proteins, is a major component of innate immunity that functions to recognize and eliminate invading pathogens ( 9 ). (asm.org)
  • 4 Under normal pregnancy conditions, the fetus is protected from maternal immune responses through an array of mechanisms, including trophoblast expression of complement regulatory proteins that inhibit complement at different steps of the activation cascade. (ahajournals.org)
  • Complement proteins fall into three broad categories, although some complement proteins may actually fit into two of these categories. (asmscience.org)
  • The first category encompasses the complement serum proteins, which react with foreign bodies in either an antibody-dependent or antibody-independent manner. (asmscience.org)
  • Host phagocytes, such as neutrophils and macrophages, have receptor proteins on their cell surfaces that specifically recognize portions of the antibody molecule (Fc receptors), fragments of complement (C3 receptors), and fibronectin. (asmscience.org)
  • Immune cells attracted to such sites expose cell surface receptor proteins that recognize particular fragments of C3 and fulfill the biologic function of phagocytosis. (asmscience.org)
  • There is positive immunostaining for complement proteins C3, C5 and C9 in the glomeruli, but no evidence of immunoglobulin or C1q deposition. (biologists.org)
  • Serum levels of complement proteins C3 and C4 are typically normal, even during acute episodes of macroscopic haematuria. (biologists.org)
  • The complement system is an enzyme cascade that is a collection of blood and cell surface proteins to help the abilities of antibodies to clear pathogens from an organism. (sinobiological.com)
  • The complement system that comprises 30 different proteins, including serum proteins, serosal proteins, and cell membrane receptors is an important part of the innate immune system. (sinobiological.com)
  • Some complement proteins bind to immunoglobulins or to membrane components of cells. (sinobiological.com)
  • Others are proenzymes that, when activated, cleave one or more other complement proteins and initiate an amplifying cascade of further cleavages. (sinobiological.com)
  • During inflammation, vascular permeability is increased by various proteolytic events, such as the generation of bradykinin, that augment local tissue responses by enabling tissue penetration of serum proteins, including complement and acute-phase proteins. (sciencemag.org)
  • Of the proteins identified in normal skin, about half were cleaved, and phorbol ester-induced inflammation increased the proportion of cleaved proteins, including chemokines and complement proteins, that were processed at previously uncharacterized sites. (sciencemag.org)
  • Complement acts as a danger‐sensing system in the innate immune system, and its activation initiates a strong inflammatory response and cleavage of the proteins C3 and C5 by proteolytic enzymes, the convertases. (embopress.org)
  • Activation of the proteolytic complement cascade triggers cleavage of the homologous 185-200 kDa proteins C3, C4, and C5 ( Supplementary Figure S1 ). (embopress.org)
  • In vivo, regulation of complement at the C3 and C5 activation steps is provided by both plasma and membrane proteins. (justia.com)
  • The plasma protein inhibitors are factor H and C4-binding protein, and the regulatory membrane proteins located on cell surfaces are complement receptors 1 (CR1), decay-accelerating factor (DAF), and membrane cofactor protein (MCP). (justia.com)
  • These proteins inhibit the C3 and C5 convertases (multi-subunit proteases), by promoting dissociation of the multisubunit complexes and/or by inactivating the complexes through proteolysis (catalyzed by factor I). Several pharmacological agents that regulate or modulate complement activity have been identified by in vitro assay, but most have been shown in vivo to be of low activity or toxic. (justia.com)
  • C3b has most important opsonizing activity Inflammation - by attracting macrophages and neutrophils Membrane attack - by rupturing cell wall of bacteria Overview[ edit ] Most of the proteins and glycoproteins that constitute the complement system are synthesized by hepatocytes. (rhein-main-verzeichnis.info)
  • Western blot: 1) 0.1 µg of purified Human C3 protein, and 2) 10 µg of normal Human serum proteins was stained with ARG10707 anti-Complement C3 (alpha chain, anaphylatoxin) antibody [6B1] at 1:5000 dilution. (arigobio.com)
  • Most complement proteins are zymogens which are proteases that become activated when cleaved. (davidson.edu)
  • C3b is a membrane associated protein which binds covalently to other complement proteins already on the pathogen surface. (davidson.edu)
  • The complex of complement proteins on the cell surface after C3b binds forms the C5 convertase. (davidson.edu)
  • After cleavage C5b interacts nonenzymatically with other complement proteins to form the MAC. (davidson.edu)
  • The binding domain of C5b for other complement proteins such as C6 and C7 has been recently characterized and is homologous to a complement binding domain on C3 and C4. (davidson.edu)
  • Other complement proteins such as C6 and C7 interact with C5 at the active site C345C in forming the MAC. (davidson.edu)
  • Bioinformatics analysis was performed to determine the function of the identified proteins (gene ontology and pathway analysis). (ajas.info)
  • We used fluorescent microscopy, monospecific antibodies against complement components, fluorescent secondary antibodies, and the analysis of .150 images to quantify the attachment of HUVEC-released complement proteins to ULVWF strings secreted by, and anchored to, the HUVECs (under conditions of ADAMTS-13 inhibition). (rice.edu)
  • It is composed of plasma and membrane proteins that complement antibody-mediated immunity through activation by three pathways. (lecturio.com)
  • Complement proteins C1-9 are named after C as complement and numbers in order of activation, except that C4 is activated before C2. (lecturio.com)
  • Serum sickness is an example of immune complex clearance by complement proteins. (lecturio.com)
  • The complement protein fragments with the lowest number attach to the target and act to activate other proteins. (lecturio.com)
  • VCP contains 4 short consensus repeat domains (SCR) that are also present in eukaryotic complement regulatory proteins ( 9 ). (asm.org)
  • Thus, the poxvirus complement control proteins might be attractive therapeutic targets to treat poxvirus infections. (asm.org)
  • Growing evidence suggests that complement proteins not only serve as mediators of innate immune defense against foreign pathogens but can also modulate diverse developmental processes, such as cell survival, growth, and differentiation in various tissues ( 1 , 2 ). (rupress.org)
  • Complement C3 (MW: 183 kDa) is one of the most abundant plasma proteins. (uiowa.edu)
  • The complement system is a part of the immune system, consists of a series of proteins that interact with one another in a highly regulated manner, in order to eliminate pathogens. (microbeonline.com)
  • Complements are soluble proteins and glycoproteins mostly produced by hepatocytes . (microbeonline.com)
  • The C-terminal fragment C2a consisting of a serine protease (SP) and a von Willebrand factor type A (vWFA) domain, remains attached to C4b, forming the C3 convertase, C4b2a. (rcsb.org)
  • The assembly of C3 convertases (C4b2a and C3bBb) is a prerequisite for complement activation. (nih.gov)
  • Here we describe the identification of staphylococcal complement inhibitor, an excreted 9.8-kilodalton protein that blocks human complement by specific interaction with C4b2a and C3bBb. (nih.gov)
  • C3 convertase (C4bC2b, formerly C4b2a) belongs to family of serine proteases and is necessary in innate immunity as a part of the complement system which eventuate in opsonisation of particles, release of inflammatory peptides, C5 convertase formation and cell lysis. (wikipedia.org)
  • C3 convertase can be used to refer to the form produced in the alternative pathway (C3bBb) or the classical and lectin pathways (C4bC2b, formerly C4b2a). (wikipedia.org)
  • The larger C2b produced by C2 hydrolysis attaches to the C4b to form the classical C3 convertase, C4b2b (formerly called C4b2a). (wikipedia.org)
  • One form of C3-convertase, also known as C4b2a, is formed by a heterodimer of activated forms of C4 and C2. (wikipedia.org)
  • The two activated C1s subunits are then able to catalyze the assembly of the C3 convertase (complement C4b2a) from complements C2 and C4. (sigmaaldrich.com)
  • The C1-complex cleaves C2 and C4, which then form C3 convertase (C4b2a). (sinobiological.com)
  • Proteolysis of C4 is also triggered via recognition of microbial carbohydrates in the lectin pathway (LP). C4b combines with C2 and subsequent cleavage of C2 to C2a results in generation of the LP/CP C3 convertase C4b2a. (embopress.org)
  • C4b2a is the widely used short‐hand nomenclature for the C4b-C2a complex in the complement field, and similar nomenclature is used for the remaining complexes in the following). (embopress.org)
  • The classical mannose binding lectin activation pathway leads to the C3 convertase C4b2a. (vwr.com)
  • Activated C1s protease forwards the activation signal by cleaving C4 and C4bassociated C2 to form C3 convertase C4b2a, so an inhibitor that targets the C1s protease domain could block the activation of the classical pathway of CS. (chemaxon.com)
  • The remaining α chain fragment C4b is the major activation product and is an essential subunit of the C3 convertase (C4b2a) and the C5 convertase (C3bC4b2a) enzymes of the classical complement pathway. (adipogen.com)
  • C4b and C2a form together C4b2a, which is known as the C3 convertase . (lecturio.com)
  • C4 nephritic factor (C4Nef) is an autoantibody to the classical pathway C3 convertase (C4b2a). (uiowa.edu)
  • By stabilizing C4b2a, it prolongs the half-life of this convertase and protects C4b2a against decay dissociation by C4 binding protein (C4BP). (uiowa.edu)
  • The C4b2a complex is also known as C3 convertase as this converts C3 into an active form by separating C3a and C3b. (microbeonline.com)
  • One molecule of C4b2a can cleave a large number of C3 molecules. (microbeonline.com)
  • As a highly active and small soluble protein that acts exclusively on surfaces, staphylococcal complement inhibitor may represent a promising anti-inflammatory molecule. (nih.gov)
  • It is a membrane protein and regulates also C5 convertase of the classical and alternative pathway. (wikipedia.org)
  • C4 binding protein (C4BP) interferes with the assembly of the membrane-bound C3 convertase of the classical pathway. (wikipedia.org)
  • One hybrid protein, HC3-1496, is shown to be effective in reducing complement-mediated damage in two disease models in mice, collagen-induced arthritis and myocardial ischemia/reperfusion injury. (springer.com)
  • Depletion of plasma complement in vivo by a protein of cobra venom: its effect on various immunologic reactions. (springer.com)
  • Complement component 3, often simply called C3, is a protein of the immune system. (wikipedia.org)
  • Several crystallographic structures of C3 have been determined and reveal that this protein contains 13 domains. (wikipedia.org)
  • The C3 precursor protein is first processed by the removal of 4 Arginin residues, forming two chains, beta and alpha, linked by a disulfide bond. (wikipedia.org)
  • Binding of the central complement protein C3 to wild-type immature thymocytes required the lectin but not the classical pathway. (jimmunol.org)
  • The complement system is an integral component of innate immunity and consists of soluble protein fragments and complexes found in the circulation ( 1 - 4 ). (jimmunol.org)
  • C4BPA (Complement Component 4 Binding Protein Alpha) is a Protein Coding gene. (genecards.org)
  • The classical pathway can be initiated by the binding of C1q, the first protein in the complement cascade, directly to the pathogen surface. (nih.gov)
  • The mannan-binding lectin pathway ( MB-lectin pathway ) is initiated by binding of the mannan-binding lectin, a serum protein, to mannose-containing carbohydrates on bacteria or viruses. (nih.gov)
  • Complement component C4 is a central protein in the classical and lectin pathways within the complement system. (rcsb.org)
  • Meri T, Blom A, Hartmann A, Lenk D, Meri S, Zipfel P. The hyphal and yeast forms of Candida albicans bind the complement regulator C4b-binding protein. (labome.org)
  • Background- Because complement-mediated vascular injury participates in atherosclerosis and C-reactive protein (CRP) can activate the complement cascade, we sought to determine whether CRP affects the expression of the protective complement-inhibitory factors on the cell surface of endothelial cells (ECs). (ahajournals.org)
  • Strongylocentrotus purpuratus (Purple sea urchin) has an atypical factor B with a five-module complement control protein domain. (ebi.ac.uk)
  • Recombinant protein encompassing a sequence within the center region of human Complement C2. (genetex.com)
  • There was increased binding of the classical pathway mediators immunoglobulin G (IgG) and C-reactive protein (CRP) to unencapsulated S. pneumoniae , indicating that the capsule could inhibit classical pathway complement activity by masking antibody recognition of subcapsular antigens, as well as by inhibiting CRP binding. (asm.org)
  • Crry (complement receptor 1-related protein/gene y) is a key cellular complement regulator in rodents. (rupress.org)
  • Factor H (FH) is the major regulatory protein of the complement alternative pathway, with a structure consisting of a tandem array of 20 homologous units, called short consensus repeats (SCR). (asnjournals.org)
  • Complement protein factor H (FH) is a regulatory protein of the alternative pathway. (asnjournals.org)
  • FH is a single-chain serum glycoprotein of 150 kD with a modular structure consisting of a tandem array of 20 homologous units of about 60 amino acid residues each ( 1,2 ⇓ ), called either short consensus repeats (SCR) or complement control protein. (asnjournals.org)
  • C2 (Complement C2) is a Protein Coding gene. (genecards.org)
  • The protein mediates cellular binding to particles and immune complexes that have activated complement. (nih.gov)
  • Complement factor H related protein 5 (CFHR5) nephropathy is a monogenic disorder of complement regulation that is endemic in Cyprus. (biologists.org)
  • Its identification suggests a role for the CFHR5 protein in the regulation of complement in the kidney. (biologists.org)
  • CRP is an acute-phase serum protein and a mediator of innate immunity through the complement activation of C1, C4, C2 and C3 components. (biomedcentral.com)
  • Compounds comprising peptides and peptidomimetics capable of binding the C3 protein and inhibiting complement activation are disclosed. (justia.com)
  • In particular, this invention provides peptides and peptidomimetics capable of binding the C3 protein and inhibiting complement activation. (justia.com)
  • C3 is an acute phase protein that is produced by a wide range of tissues, including renal epithelial cells and hepatocytes. (vwr.com)
  • Human C4 is the most polymorphic protein of the complement system. (adipogen.com)
  • A peptide (C3a) derived from the encoded protein has antimicrobial activity, so people with C3 deficiency are susceptible to bacterial infection. (arigobio.com)
  • Before being secreted as a mature protein, C3 is split into β-chain (645 residues and 70 kDa) and α-chain (992 residues and 115 kDa) and forms a rare internal thioester bond. (adipogen.com)
  • The short isoform has B-cell stimulatory activity.C3-beta-c: Acts as a choattractant for neutrophils in chronic inflammation.Acylation stimulating protein: adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes, regulating fat storage and playing a role in postprandial TG clearance. (enquirebio.com)
  • The complement system consists of a series of plasma protein interactions which mediate direct attack on pathogens (opsonization) and induce inflammation. (davidson.edu)
  • Background: Vascular endothelial cells (ECs) express and release protein components of the complement pathways, as well as secreting and anchoring ultra-large von Willebrand factor (ULVWF) multimers in long string-like structures that initiate platelet adhesion during hemostasis and thrombosis. (rice.edu)
  • The vaccinia virus complement control protein (VCP) is secreted by infected cells and has been shown to inhibit complement activation through interactions with C3b/C4b. (asm.org)
  • The vaccinia virus complement control protein (VCP) is a 35-kDa protein that is encoded by the C3L gene and secreted by cells infected with vaccinia virus ( 7 , 8 ). (asm.org)
  • The mature protein is composed of two disulfide-bound polypeptide chains (C3α and C3β). (uiowa.edu)
  • In these patients, the type of complement-associated defect cannot be predicted by measuring plasma protein levels but may be discoverable by genetic analysis. (uiowa.edu)
  • Daha MR and van Es LA: Relative resistance of the F-42-stabilized classical pathway C3 convertase to inactivation by C4-binding protein. (uiowa.edu)
  • Severe DENV disease (DHF/DSS) is thought to follow a complex relationship between distinct immunopathogenic processes involving host and viral factors, such as the serotype cross-reactive antibody-dependent enhancement (ADE), the activation of T cells and complement pathways, the phenomenon of the cytokine storm, and the newly described viral toxin activity of the nonstructural protein 1 (NS1), which together play critical roles in inducing vascular leak and virus pathogenesis. (intechopen.com)
  • Cleavage of complement C3 by a free floating convertase, thrombin, plasmin or even a bacterial enzyme leads to formation of C3a and C3b fragments. (wikipedia.org)
  • The C3 convertase formed in the classical or lectin pathways is formed of C4b and C2b instead (NB: C2b, the larger fragment of C2 cleavage, was formerly known as C2a). (wikipedia.org)
  • It catalyzes the proteolytic cleavage of C3 into C3a and C3b, generated during activation through the classical pathway as well as the lectin pathway. (wikipedia.org)
  • Lectin pathway activation of C3 is known to involve target recognition by mannan-binding lectin (MBL) or ficolins and generation of classical pathway C3 convertase via cleavage of C4 and C2 by MBL-associated serine protease 2 (MASP-2). (nih.gov)
  • The complement system is a complex cascade involving proteolytic cleavage of serum glycoproteins often activated by cell receptors. (sigmaaldrich.com)
  • In the alternate pathway complement C3 undergoes spontaneous cleavage resulting in complement B binding to C3b. (sigmaaldrich.com)
  • In such a cascade, an active complement enzyme generated by cleavage of its zymogen precursor then cleaves its substrate, another complement zymogen, to its active enzymatic form. (nih.gov)
  • Activated cleavage products C2A and C4B combine to form C3 convertase, which cleaves C3. (wikipathways.org)
  • The cleavage product C3B joins the complex to form C5 convertase, which cleaves C5. (wikipathways.org)
  • Moreover, C4b provides a platform for assembly of the proteolytically active convertases that mediate downstream complement activation by cleavage of C3 and C5. (rcsb.org)
  • Cleavage of native C3 by the C3 convertase results in the release of the C3a anaphylatoxin. (els.net)
  • this cleavage leads to the binding of the resulting C3 fragments to the cell membrane through reaction of membrane acceptors with the carbonyl group of C3 revealed after disruption of the intramolecular thioester bond. (biochemj.org)
  • In all three pathways, C3-convertase cleaves and activates component C3, creating C3a and C3b, and causes a cascade of further cleavage and activation events. (technologynetworks.com)
  • Cleavage of serum IgG by the enzyme IdeS reduced C3b/iC3b deposition on all of the strains, but there were still marked increases in C3b/iC3b deposition on unencapsulated TIGR4 and D39 strains compared to encapsulated strains, suggesting that the capsule inhibits both IgG-mediated and IgG-independent complement activity against S. pneumoniae . (asm.org)
  • Cleavage of the C3 component by either the classical pathway or the alternative pathway releases C3a and C3b. (genetex.com)
  • Cleavage of C5 requires complement fragment C3b which binds C5 and renders it susceptible to cleavage by the C4b,2a complex. (qmul.ac.uk)
  • Here, we demonstrate that mice deficient in complement receptor 3 (CR3) (CD11b −/− ), a signaling receptor activated by multiple ligands including the C3 cleavage fragment iC3b, develop less-severe disease signs and decreased tissue destruction compared to RRV-infected wild-type mice. (asm.org)
  • The proteolytic processing of C3 generates an array of cleavage products that are involved in the amplification of complement activity through the formation of C3 and C5 convertases, the opsonization of pathogens, and the attraction and activation of leukocytes of both the innate and adaptive arms of the immune response. (asm.org)
  • Both the classical and the lectin pathway share the identical C3 and C5 convertase complexes formed after cleavage of C4 by either activated C1s (classical pathway) or activated MASP-2 (lectin pathway) (see 1) and subsequent cleavage and activation of C4b-bound C2 through activated C1s or MASP-2 (see 2). (asmscience.org)
  • Acts also in the inhibition of spontaneous complement activation by impairing the formation and function of the alternative and classical pathway C3/C5 convertases, and by serving as a cofactor for the cleavage by factor I of C3b to iC3b, C3c and C3d,g, and of C4b to C4c and C4d (PubMed:2972794, PubMed:8175757). (nih.gov)
  • The classical pathway (CP) is activated by surface‐bound immune complexes, resulting in cleavage of C4 and thereby generation of C4b ( Figure 1A ). (embopress.org)
  • Production of C3-convertase leads to cleavage of C3 into C3a and C3b and C3b joins with the C3 convertase to make C5 convertase. (adipogen.com)
  • C5-C345C also interacts with C5 convertase although it is not the cleavage site. (davidson.edu)
  • This diagram of C5 convertase shows where C5 is cleaved (dotted arrows) to become activated and where the functional C5-C345C domain is relative to the cleavage site. (davidson.edu)
  • The three complement activation pathways (alternative, classical, lectin) converge at the stage of C3 cleavage to generate the activated form of C3, which is C3b. (uiowa.edu)
  • Here, we present the crystal structure of Mg(2+)-bound C2a to 1.9 A resolution in comparison to its homolog Bb, the catalytic subunit of the alternative pathway C3 convertase, C3bBb. (rcsb.org)
  • Thus, the alternative C3 convertase (C3bBb) is formed and is able to cleave C3 via its dimeric Bb subunit. (wikipedia.org)
  • Properdin (Factor P) is the only known positive regulator of complement activation that stabilizes the alternative C3 convertase (C3bBb). (wikipedia.org)
  • In the alternative complement pathway, C3 is cleaved by C3bBb, another form of C3-convertase composed of activated forms of C3 (C3b) and factor B (Bb). (wikipedia.org)
  • The resultant complex, C3bBb, is called the alternative pathway (AP) C3 convertase. (wikipedia.org)
  • Diffusion of the Ba subunit results in an active alternate pathway C3 convertase (C3bBb). (sigmaaldrich.com)
  • C3bBb is stabilized by binding to properdin prior to merging into the common pathway and conversion of C3. (sigmaaldrich.com)
  • Screening of well-characterized complement-binding molecules revealed that differential inhibition of AP C3 convertases (C3bBb) and C5 convertases [C3bBb(C3b) n ] is possible. (frontiersin.org)
  • By demonstrating that the fluid phase convertase C3bBb is sufficient to cleave C5 as long as C5 is bound on C3b/C4b-decorated surfaces, we show that surface fixation is necessary only for the C3b/C4b opsonins that prime C5 but not for the catalytic convertase unit C3bBb. (onmedica.com)
  • C3bBb acts as C3 convertase which cleaves C3 - this creates a continuous loop and many C3b can be deposited on the invader's cell surface. (epomedicine.com)
  • Decay Accelerating Factor (DAF) accelerates destruction of C3 convertase (C3bBb). (epomedicine.com)
  • The alternative pathway (AP) C3 convertase C3bBb is formed when factor B (fB) combines with C3b, after which fB is activated by factor D (fD) ( Figure 1A ). (embopress.org)
  • It is central to the alternative pathway that leads to the C3 convertase C3bBb. (vwr.com)
  • This was verified when non-functional FB blocked the formation of AP C3 convertase complexes (C3bBb) on ULVWF strings. (rice.edu)
  • Since C3 convertases cleave C3 to produce C3b which can then form an additional C3 convertase through the alternative pathway, this is a potential mechanism of signal amplification in the complement cascade resulting in the deposition of large numbers of C3b molecules on the surface of activating particles, enabling opsonisation and acute local inflammation. (wikipedia.org)
  • C5 convertases cleave C5 into chemoattractant C5a, and C5b, which drives formation of the membrane attack complex. (frontiersin.org)
  • Convertase enzymes fulfill a central role in the complement cascade as they cleave C3 and C5, which mediate nearly all complement effector functions. (frontiersin.org)
  • C3 convertases cleave C3 into C3a, a chemoattractant molecule, and C3b, which covalently binds to target surfaces and triggers phagocytosis. (frontiersin.org)
  • C5 convertases cleave C5 into C5a, a potent mediator of leukocyte recruitment and inflammation, and C5b, the initiator of the membrane attack complex and cell lysis. (frontiersin.org)
  • MBL-associated serine proteases MASP1 and MASP1 can cleave C2 and C4 in place of the C1 complex, leading to the formation of C3 convertase and the subsequent cascade. (wikipathways.org)
  • C3 convertases generated by all pathways are able to cleave C3 into C3a and C3b, latter of which forms additional convertases, thereby rapidly amplifying complement response. (els.net)
  • The MBL-associated serine proteases, MASP-1, and MASP-2, are activated and cleave C4 and C2, which then form the C3 convertase as in the classical pathway. (sinobiological.com)
  • These convertases cleave C3 resulting in C3a and C3b. (vwr.com)
  • Both C5 convertases perform the same function, which is to cleave C5 into its two active components C5a and C5b. (davidson.edu)
  • however, in two patients with nephritic factor in their serum fractional catabolism of C5 was normal despite markedly increased C3 turnover, suggesting that in patients with alternative pathway activation by nephritic factor little or no C5 convertase is generated. (curehunter.com)
  • To test this, thymocytes and fresh serum were separately obtained and incubated together in vitro to assess complement deposition. (jimmunol.org)
  • The capacity of serum to support C3 deposition was examined by ELISA using microtiter plates coated with O antigen-specific oligosaccharides derived from Salmonella typhimurium, S. thompson, and S. enteritidis corresponding to serogroups B, C, and D (BO, CO, and DO). (nih.gov)
  • C3 deposition onto wells coated with O antigen-specific BO, CO, and DO following incubation in PNHS or C2-deficient serum. (nih.gov)
  • C3 deposition induced by CO antigen (1,000 ng/well) in an MBL-deficient serum that was depleted of C1qDP and Igs. (nih.gov)
  • The serum was used at a final concentration of 20% and was studied with or without reconstitution of the alternative pathway. (nih.gov)
  • An earlier study ( 10 ) reported that Cremophor EL, the commonly used solvent for paclitaxel, but not the paclitaxel itself, activates complement in vitro after incubation with serum. (jimmunol.org)
  • Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. (genetex.com)
  • As shown by SDS/polyacrylamide-gel electrophoresis, the intracellular pro-C3 (200 kDa) and the extracellular secreted C3 (alpha-chain 110 kDa and beta-chain 75 kDa) are identical with the forms of C3 previously characterized from human serum. (biochemj.org)
  • Unencapsulated strains were more susceptible to neutrophil phagocytosis after incubation in normal serum, normal serum treated with IdeS, complement-deficient serum, and complement-deficient serum treated with IdeS or in buffer alone, suggesting that the capsule inhibits phagocytosis mediated by Fcγ receptors, complement receptors, and nonopsonic receptors. (asm.org)
  • Fig1: Western blot analysis on human serum using anti-complement C3 polyclonal antibody. (bonopusbio.com)
  • C3 nephritic factor and C4 nephritic factor in the serum of two patients with hypocomplementaemic membranoproliferative glomerulonephritis. (uiowa.edu)
  • Serum serine proteases which participate in COMPLEMENT ACTIVATION. (bioportfolio.com)
  • More than 20 types of complements are present in serum, found circulating normally in human body in inactive forms (called as zymogens or proenzymes) . (microbeonline.com)
  • The multi-domain serine protease C2 provides the catalytic activity for the C3 and C5- convertases of the classical and lectin pathways of complement activation. (rcsb.org)
  • Classical, Alternate and Lectin Pathways. (sigmaaldrich.com)
  • Activation of the complement cascade through the classical, alternative or lectin pathways thus generating opsonins like C3b and C5b, anaphylatoxins C3a and C5a, chemotaxin, and inflammatory mediators, which leads to cellular death. (biomedcentral.com)
  • Its activation through the classical, alternative or lectin pathways leads to the generation of anaphylatoxic peptides C3a and C5a and formation of the C5b-9 membrane attack complex. (justia.com)
  • We found that HUVEC-released C4 did not attach to ULVWF strings, ruling out activation of the classical and lectin pathways by the strings. (rice.edu)
  • The complement system has been considered for a long time as a simple lytic cascade, aimed to kill bacteria infecting the host organism. (frontiersin.org)
  • Complement cascade is activated immediately after encountering the pathogen. (frontiersin.org)
  • Emerging evidence over the last decade unexpectedly identified the complement cascade as a common thread in this process. (jci.org)
  • Emerging evidence over the past 15 years supports the concept that the complement cascade, traditionally considered a component of innate immunity, unexpectedly regulates kidney IR injury, T cell and humoral alloimmunity that underlie transplant rejection, and progressive kidney injury that results in late graft failure. (jci.org)
  • Ischaemic infarction may also cause initiation of the complement cascade. (sigmaaldrich.com)
  • The alternate pathway does not require the action of antibodies to inititate the cascade, but is initiated by foreign cell surface components. (sigmaaldrich.com)
  • The complement system activates through a triggered-enzyme cascade. (nih.gov)
  • In the early phases of an infection, the complement cascade can be activated on the surface of a pathogen through any one, or more, of the three pathways shown in Fig. 2.8 . (nih.gov)
  • Complement recognizes microbes or damaged host cells and subsequently triggers an enzymatic cascade that mainly serves to (a) label target cells for phagocytosis by immune cells, (b) produce chemoattractants, and (c) directly kill target cells via pore formation ( 2 ). (frontiersin.org)
  • The complement cascade begins via specific recognition of target cells in the classical (CP) and lectin (LP) pathways. (frontiersin.org)
  • It is well established that activation of the complement cascade alters functional responses of neutrophils (PMN) in the course of systemic inflammation and contributes to the development of organ failure [ 15 , 23 ]. (hindawi.com)
  • Furthermore, potential therapeutic strategies targeting the complement cascade to prevent the development of MOF as well as possible future research directions are addressed. (hindawi.com)
  • The complement system is a biochemical cascade that helps, or complements, the ability of antibodies to clear pathogens from an organism. (wikipathways.org)
  • Activation of complement cascade via the antibody-mediated classical pathway can initiate red blood cell (RBC) destruction, causing transfusion reactions and hemolytic anemia. (bloodjournal.org)
  • 11 DAF prevents the formation and accelerates the decay of the C3 and C5 convertases that act early within the complement cascade, 11 functioning to maintain vascular integrity as a key protector against complement-mediated cell lysis. (ahajournals.org)
  • Indeed, complement acts as a rapid and efficient immune surveillance system that has distinct effects on healthy and altered host cells and foreign intruders through a complex cascade of proteases [ 1 ]. (intechopen.com)
  • The end result of this complement activation or complement fixation cascade is stimulation of phagocytes to clear foreign and damaged material, proxy inflammation to attract additional phagocytes, and activation of the cell-killing membrane attack complex. (technologynetworks.com)
  • All of the 3 pathways converge at a particular point in the cascade and produces a common complex called C3-convertase which cleaves the C3 component of the complement system. (epomedicine.com)
  • Activation of the complement system results in a cascade of enzymatic proteolysis of various components of the complement system, including complement component 3 (C3), C4, and C5. (asm.org)
  • The complement activation is tightly regulated by membrane-bound and fluid-phase regulatory components to avoid runaway activation of the enzymatic cascade that could lead to excess host tissue damage, inflammation, and depletion of complement components. (asmscience.org)
  • The complement cascade is activated in normal pregnancy, and excessive complement activation propagates the systemic inflammatory response in severe preeclampsia. (ahajournals.org)
  • Diagram of the complement cascade, which consists of enzymatic steps involving a number of inactive proenzymes (or zymogens). (asmscience.org)
  • Model shows active mediators of the complement cascade during inflammation in airway asthma. (biomedcentral.com)
  • This invention relates to activation of the complement cascade in the body. (justia.com)
  • C3 is a central factor in the complement cascade. (vwr.com)
  • Reaction Cascade of the Complement System: Classical complement pathway The classical and alternative complement pathways The classical pathway is triggered by activation of the C1-complex. (rhein-main-verzeichnis.info)
  • Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. (abcam.cn)
  • The Classical Complement Cascade Mediates CNS Synapse Elimination. (freepatentsonline.com)
  • It binds as a cofactor to C3b/C4b inactivator (C3bINA), which then hydrolyzes the complement fragment C4b. (genecards.org)
  • Finally, the alternative pathway can be initiated when a spontaneously activated complement component binds to the surface of a pathogen. (nih.gov)
  • In the alternative pathway, C3b binds to Factor B. Factor D releases Factor Ba from Factor B bound to C3b. (technologynetworks.com)
  • C5 convertase is also formed by the Classical Pathway when C3b binds C4b and C2a. (technologynetworks.com)
  • describes the use of a phage-displayed combinatorial random peptide library to identify a 27-residue peptide that binds to C3 and inhibits complement activation. (justia.com)
  • The monoclonal antibodies binds strongly and cleanly to a band at about 115 kDa which represents the intact α subunit of C3 and various proteolytic bands at approximately 68 and 48 kDa. (arigobio.com)
  • Most of C4b attaches to the target cells while only a few binds to C2a to form C3 convertase. (lecturio.com)
  • VCP inhibits activation of complement, binds C4b and C3b, acts as a cofactor in the enzymatic inactivation of C4b and C3b by factor I, prevents the formation of the classical and alternative pathway C3 convertases, and accelerates their decay ( 6 , 12 , 15 , 18 ). (asm.org)
  • It binds to carbohydrate groups on invading pathogens and plays a key role in the MANNOSE-BINDING LECTIN COMPLEMENT PATHWAY. (bioportfolio.com)
  • and the C5 convertase, which cleaves C5 into C5a and C5b.C3b, thus formed, binds C3 convertase to form C5 convertase. (microbeonline.com)
  • Classical pathway , activated by antigen-antibody reaction, Alternative pathway , activated on microbial cell surfaces, and Mannose binding Lectin pathway , activated by a plasma lectin that binds to mannose residues on microbes. (microbeonline.com)
  • C3b binds to the microbial surface or to the convertase itself. (microbeonline.com)
  • C3b when binds to C3 convertase forms C4bC2aC3b ( C5 convertase ) which activates C5. (microbeonline.com)
  • The Lectin pathway involves mannose-binding lectin (MBL) binding the surface of the pathogen instead of C1Q. (wikipathways.org)
  • The components of complement system can be organised into three major pathways: The classical pathway is mainly initiated by the binding of C1q to antigen-antibody complexes, whereas the lectin pathway is triggered by binding of mannose‐binding lectin ( MBL ) or ficolins to glycosylated surfaces on microbial cell walls. (els.net)
  • The mannose-binding lectin pathway can be activated by C3 hydrolysis or antigens without the presence of antibodies (non-specific immune response). (technologynetworks.com)
  • The complement system has four major function, including lysis of infectious organisms, activation of inflammation, opsonization and immune clearance.There are three different complement pathways, the classical complement pathway, the alternative complement pathway, and the mannose-binding lectin pathway. (sinobiological.com)
  • The complement system is a part of the larger immune system and three biochemical pathways are present: the classical complement pathway, the alternative pathway, and the mannose-binding lectin pathway. (adipogen.com)
  • The mannose-binding lectin-associated serine proteases (MASP)-1 and -2 activate the lectin pathway of the complement system. (bioportfolio.com)
  • High levels of mannose-binding lectin (MBL), an activator of a part of the immune system called the complement system, have been associated with increased mortality and risk of early signs. (bioportfolio.com)
  • C3b, the larger fragment, becomes covalently attached to the microbial surface or to the antibody molecules through the thioester domain at the site of complement activation. (wikipedia.org)
  • Complement C3b may be an opsonin for antigen-antibody complexes which helps prevent damage from the formation of large, insoluble immune aggregates. (sigmaaldrich.com)
  • The classical pathway mediates specific antibody responses. (sigmaaldrich.com)
  • Subsequent binding of the antibody to complement C1q subunits of C1 result in catalytically active C1s subunits. (sigmaaldrich.com)
  • This activity was said to ' complement ' the antibacterial activity of antibody , hence the name. (nih.gov)
  • Although first discovered as an effector arm of the antibody response, complement can also be activated early in infection in the absence of antibodies. (nih.gov)
  • 2 Generally, in the presence of a potent, complement-binding antibody and large numbers of closely situated red cell antigens, complement activation can proceed to completion, resulting in intravascular hemolysis. (bloodjournal.org)
  • Although antibody-coated red cells can also be destroyed extravascularly without complement activation, red cell removal is enhanced considerably when C3 is present on red cells in addition to immunoglobulin G (IgG). (bloodjournal.org)
  • Immunofluorescence analysis of methanol-fixed A431, using Complement C2(GTX105404) antibody at 1:200 dilution. (genetex.com)
  • The classical complement pathway typically requires antigen-antibody complexes (immune complexes) for activation (specific immune response), whereas the alternative pathway can be activated by C3 hydrolysis, foreign material, pathogens, or damaged cells. (technologynetworks.com)
  • We conclude that constrained scattering modelling makes useful contributions to our understanding of antibody and complement structure and function. (royalsocietypublishing.org)
  • The complement system provides innate defense against microbial infection and is a "complement" to antibody mediated immunity. (genetex.com)
  • This antibody has also been reported to recognize the C3 fragments, C3a, C3b, and C3c. (genetex.com)
  • The classic complement pathway is triggered when antibody-antigen complex interact with C1-complex, which consists of C1q, two molecules of C1r, and two molecules of C1s. (sinobiological.com)
  • To date, there are no inhibitors of complement activation used in the clinic, though certain candidates for clinical use exist, specifically, a recombinant form of complement receptor 1 known as soluble complement receptor 1 (sCR1) and a humanized monoclonal anti-05 antibody (5G1.1-scFv). (justia.com)
  • The classical pathway is initiated by the activation of the C1-complex (C1q, C1r and C1s) by C1q's binding to antibody-antigen. (adipogen.com)
  • Immune complexes can activate complement deposition on the antibody portion of the immune complexes leading to further activation of phagocytic and hematopoietic cells that clear the immune complexes from the circulation. (lecturio.com)
  • VCP inhibits the antibody-dependent, complement-enhanced neutralization of vaccinia virus virions ( 3 ). (asm.org)
  • Complement activation is triggered by an antibody when it is bound to the antigen. (microbeonline.com)
  • The classical pathway begins with the formation of antigen-antibody complex (immune complex). (microbeonline.com)
  • Hence, the antibody activates the complement system only when bound to an antigen. (microbeonline.com)
  • Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. (abcam.com)
  • Potential roles in the proteolytic activation of C3 and C5 have also been assigned to noncomplement proteinases, including enzymes of the coagulation and fibrinolysis cascades. (els.net)
  • Proteolytic and nonproteolytic activation of C3. (els.net)
  • Preliminary evidence for a cell-associated proteolytic activity specific for C3 is given, as well as for a covalent-like binding of C3 fragments to the cell membranes. (biochemj.org)
  • After activation C3b can bind covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates.Derived from proteolytic degradation of complent C3, C3a anaphylatoxin is a mediator of local inflammatory process. (enquirebio.com)
  • After generation of pathogen-specific antibodies, complement contributes in the clearance of immune complexes and pathogen elimination. (frontiersin.org)
  • The activation pathways converge in the formation of C3 convertase complexes, which lead to the activation of further complement factors. (asm.org)
  • Recently, L-ficolin and H-ficolin also were found to form complexes with the MASPs and to be capable of activating complement ( 19 , 23 ). (asm.org)
  • The affinity of factor B to bind C3b is higher on "activating "surfaces, and the half-life of C3bB, C3Bb, and C3Bb(C3b)n complexes, significantly increased by the action of properdin, allows the alternative pathway amplification loop to be formed. (asmscience.org)
  • Mediates the binding by these cells of particles and immune complexes that have activated complement to eliminate them from the circulation (PubMed:2963069). (nih.gov)
  • Central to innate immunity, complement activation is heightened in pregnancy, 1 in part, to facilitate normal clearance of fetoplacental material, including apoptotic blebs, 2 circulating fetal DNA, 3 and immune complexes. (ahajournals.org)
  • The activation of the C1 complex is the „classical activation pathway" of CS, which is initiated by the interaction of C1q with immunoglobulin (Ig) antigen complexes. (chemaxon.com)
  • In contrast, C3, FB, FD, FP and C5, FH and FI attached to ULVWF strings in quantitative patterns consistent with assembly of the AP components into active complexes. (rice.edu)
  • Defects in C3 are the cause of complement component 3 deficiency (C3D) [MIM:120700]. (abcam.com)
  • Human complement component C3: cDNA coding sequence and derived primary structure. (springer.com)
  • Primary structure of cobra complement component C3. (springer.com)
  • c3 may be lost in urine in nephrotic syndrome Complement component 3 has been shown to interact with Factor H. Deficiencies in C3 lead to genetic infections, usually fatal to the newborn. (wikipedia.org)
  • These pathways converge at the complement component 3 (C3) convertase, which catalyzes formation of effector molecules, opsonins, and anaphylatoxins by enzymatic fragmentation of C3. (jimmunol.org)
  • factor B a complement component that participates in the alternative complement pathway. (thefreedictionary.com)
  • Depositions of the third component of complement (C3) with or without immunoglobulins may be observed on immunofluorescent studies [ 1 ]. (hindawi.com)
  • Complement was discovered many years ago as a heat-labile component of normal plasma that augments the opsonization of bacteria by antibodies and allows antibodies to kill some bacteria. (nih.gov)
  • Component C2 which is part of the classical pathway of the complement system is cleaved by activated factor C1 into two fragments: C2b and C2a. (uniprot.org)
  • Xaa bond in complement component C5 alpha-chain to form C5a and C5b. (uniprot.org)
  • Complement, a key component of the innate immune system, has been associated with neuroinflammation, a potentially important trigger of some types of neuropathic pain. (jimmunol.org)
  • Once activated by one of the three main pathways (i.e., the classical, lectin, or alternative pathway), C3, the central component of the complement system, is cleaved by C3 convertases to release C3a and to deposit C3b on the surface of the complement activation site. (jimmunol.org)
  • C3b is vitally contributing to the clearance of pathogens by phagocytes (macrophages and neutrophils) and is a major component of the C5 convertase, which in turn cleaves C5 to C5a and C5b. (els.net)
  • Secretion of complement component C3 by U937 cells was studied. (biochemj.org)
  • Binding of C3b to the C4b component of the C3 convertase, results in C5 convertase (C4b3b2a) formation. (genetex.com)
  • Monospecific to human C3 complement component. (genetex.com)
  • 1. Kerr, M.A. The second component of human complement. (qmul.ac.uk)
  • Previous studies using a mouse model of RRV-induced disease demonstrated that viral infection results in a severe inflammatory arthritis and myositis and that complement component 3 (C3) contributes to the destructive phase of the inflammatory disease but not the recruitment of cellular infiltrates to the sites of RRV-induced inflammation. (asm.org)
  • The complement system provides a fundamental component of the body's immune response to invading microorganisms. (asmscience.org)
  • A deficiency in any component of the classical pathway is associated with an increased risk of immunological disease and recurrent bacterial infections. (asmscience.org)
  • Complement component C3 plays a central role in activation of all three pathways. (justia.com)
  • The complement system (CS) is a key component of innate immunity, which is involved in several physiologic and pathologic processes. (chemaxon.com)
  • Complement component C4 is an essential component of humoral immune response. (adipogen.com)
  • The alternative activation pathway and complement component C3 are critical. (rhein-main-verzeichnis.info)
  • This pathway can proceed on The complement component C3 is. (rhein-main-verzeichnis.info)
  • Complement component C3 is cleaved by: A. C3b The classical and alternative pathways meet at complement component: A. C3. (rhein-main-verzeichnis.info)
  • InPaul Ehrlich renamed the heat-sensitive component "complement. (rhein-main-verzeichnis.info)
  • Ehrlich, therefore, named this heat-labile component "complement", because it is something in the blood that "complements" the cells of the immune system. (rhein-main-verzeichnis.info)
  • As C3 is the major complement component and participates in several stages of the immune response, its deficiency generally associated with higher susceptibility to severe bacterial infections and in some cases with autoimmune diseases such as systemic lupus erythematosus. (adipogen.com)
  • Immunofluorescence studies on the subcomponents of the first component of complement (C1): detection of C1q and C1s in different cells of biopsy material and on human as well as on guinea pig peritoneal macrophages. (freepatentsonline.com)
  • Complement Component 1Q (C1Q) Upregulation in Retina of Murine, Primate, and Human Glaucomatous Eyes. (freepatentsonline.com)
  • Non-enzymatic component of the C3 and C5 convertases and thus essential for the propagation of the classical complement pathway. (nih.gov)
  • The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation. (uab.edu)
  • It is a pivotal component of complement and is central to the activation cascades. (uiowa.edu)
  • C5b subsequently takes the lead in formation of the terminal C5b-9 complement complex ( TCC ), ultimately resulting into cell lysis. (els.net)
  • 9 This is supported by the presence of activated complement components in atherosclerotic plaques, such as the membrane attack complex (MAC, C5b-9), which promotes cellular activation, upregulates adhesion molecules, stimulates chemokine secretion, and can cause cell lysis. (ahajournals.org)
  • This infers resistance to complement-mediated cell lysis, allowing parasite survival and infection. (genecards.org)
  • Isoform 3 inhibits the classical complement pathway, while membrane-bound isoform 1 inhibits deposition of C3b via both the classical and alternative complement pathways. (uniprot.org)
  • The convertases catalyze C3b deposition on activator surfaces. (nih.gov)
  • Staphylococcal complement inhibitor bound and stabilized C3 convertases, interfering with additional C3b deposition through the classical, lectin and alternative complement pathways. (nih.gov)
  • In vitro, MBL2 is required for complement deposition on immature thymocytes. (jimmunol.org)
  • This blocked C3 deposition on NKAP-deficient T cells but failed to restore normal cellularity, indicating that complement contributes to clearance but is not the primary cause of peripheral T cell lymphopenia. (jimmunol.org)
  • MBL bound to CO, but not to BO and DO, and efficiently supported C3 deposition in the absence of C2, C4, or MASP-2. (nih.gov)
  • MASP-1 might contribute, but was not required for C3 deposition in the model used. (nih.gov)
  • Independent of MBL, specific antibodies to CO supported C3 deposition through classical and alternative pathways. (nih.gov)
  • C and D ) Kinetics of C3 deposition in wells coated with oligosaccharide at 1,000 ng/well. (nih.gov)
  • C3 deposition was detected with alkaline phosphatase-conjugated rabbit anti-C3c antibodies. (nih.gov)
  • C3 deposition was measured after 60 minutes at 37°C. The experiment was performed in duplicate and was repeated once with similar results. (nih.gov)
  • Membranoproliferative glomerulonephritis (MPGN) is a pattern of disease characterized by the deposition of immunoglobulins, complement factors, or both along capillary walls and within the glomerular mesangium. (hindawi.com)
  • Following transfusion of human group O RBCs into mice lacking detectable pre-existing antibodies against the transfused RBCs, systemic coadministration of 10 mg/kg sCR1, a dose well tolerated in human subjects for prevention of tissue injury, completely inhibited the in vivo clearance of the transfused RBCs and surface C3 deposition in the first hour after transfusion, correlating with the half-life of sCR1 in the circulation. (bloodjournal.org)
  • Treatment with sCR1 increased the survival of transfused human group A RBCs in the circulation of mice with pre-existing anti-A for 2 hours after transfusion by 50%, reduced intravascular hemolysis, and lowered the levels of complement deposition (C3 and C4), but not immunoglobulin G (IgG) or IgM, on the transfused cells by 100-fold. (bloodjournal.org)
  • The ultimate goal for complement activation is C3b deposition on the target cell membrane followed by the membrane attack complex (MAC) responsible for opsonization . (lecturio.com)
  • Surface bound CRP reduces deposition of and generation of C5b-9 by the alternative pathway and deposition of C3b and lysis by the lectin pathway. (nih.gov)
  • The C3 convertase activates C3 by cleaving the alpha chain, releasing C3a anaphylatoxin and generating C3b (beta chain + alpha' (alpha prime) chain). (wikipedia.org)
  • Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2. (nih.gov)
  • Upon binding to carbohydrate-based pathogen-associated molecular patterns (PAMPs) on microorganisms, MBL activates complement via the MBL-associated serine proteases (MASPs) ( 6 , 22 , 37 ). (asm.org)
  • This in turn cleaves and activates the next zymogen in the complement pathway. (nih.gov)
  • The deposited C3b facilitates phagocytosis (opsonization) of the target cells and the formation of C5 convertase, which activates C5 into C5a and C5b. (jimmunol.org)
  • In its activated form, C4b becomes a subunit of the C3 convertase, which is an enzymatic complex that activates C3 of the classical and lectin complement activation pathways. (adipogen.com)
  • Binding of CRP to these substrates activates the classical complement pathway leading to their uptake by phagocytic cells. (nih.gov)
  • The active C4bC2a activates C3. (microbeonline.com)
  • People with C3 deficiency are susceptible to bacterial infection. (wikipedia.org)
  • MBL-dependent C2 bypass activation could be particularly important in various inherited and acquired complement deficiency states. (nih.gov)
  • All but one patient exhibited alternative pathway-mediated complement consumption, with no detectable FH antigenic levels or with 50% immunochemical or functional FH levels in the case of complete or partial deficiency, respectively. (asnjournals.org)
  • Mice with dual C3 and C5 deficiency had a more exacerbated phenotype that was reversed by combined C3a and C5a reconstitution. (rupress.org)
  • Autoantibody stabilization of the classical pathway C3 convertase leading to C3 deficiency and Neisserial sepsis: C4 nephritic factor revisited. (uiowa.edu)
  • however, dysregulation of complement activation can cause onset and progression of numerous inflammatory diseases. (frontiersin.org)
  • Unwanted complement activation on the body's own cells is a key pathological driver in a wide spectrum of immune diseases including autoimmune, inflammatory, and degenerative diseases ( 3 - 5 ). (frontiersin.org)
  • In the present review, mechanisms of the inflammatory response in the development of MOF in sepsis and SIRS with particular focus on the complement system are discussed. (hindawi.com)
  • The three main consequences of complement activation are the opsonization of pathogens, the recruitment of inflammatory and immunocompetent cells, and the direct killing of pathogens. (wikipathways.org)
  • The anaphylatoxins C3a and C5a mediate the inflammatory responses of complement. (els.net)
  • 6 The burden of fetoplacental debris becomes exaggerated in severe preeclampsia, 7 - 10 propagating a systemic inflammatory response and placing strain on both classical and alternative complement signaling pathways ( Figure 1 ) as early as the first trimester. (ahajournals.org)
  • The third are cell surface receptors that bind to the products of complement activation and signal host cells to participate in inflammatory and immune reactions. (asmscience.org)
  • Further, it highlights activation of inflammatory cells (Basophils, PMNs and Macrophages) through complement receptor binding and downstream release of inflammatory mediators. (biomedcentral.com)
  • Dysregulated or impaired complement is involved in an increasing list of human diseases (e.g. autoimmune, inflammatory, and neurodegenerative diseases etc. (chemaxon.com)
  • Hence, it seems that stroke treatment needs more efficient and inflammatory-targeted compounds to modulate inflammatory-related pathways. (boswellia.org)
  • This in vivo effect is likely due in part to enhanced complement-mediated neutralization of virus lacking expression of VCP ( 3 ) as well as the recruitment of inflammatory cells to areas of active infection ( 13 ). (asm.org)
  • Complement activation by CRP may help limit the inflammatory response by providing opsonization with minimal generation of C5a and C5b-9. (nih.gov)
  • Complements are activated only during inflammatory reactions. (microbeonline.com)
  • Rosmarinic acid has been reported not to inhibit t-butyl hydroperoxide-induced paw edema in the rat, indicating selectivity for complement-dependent processes. (sigmaaldrich.com)
  • Although both convertases contain C3b, the C3b-binding molecules Efb-C/Ecb and FHR5 specifically inhibit C5 conversion. (frontiersin.org)
  • Stoichiometric C3 inhibition failed to inhibit C5 activation and lytic activity during strong classical pathway activation, demonstrating a "C3 bypass" activation of C5. (onmedica.com)
  • In the present study, we have assessed the ability of a human recombinant soluble form of complement receptor 1 (sCR1) to inhibit complement-mediated RBC destruction in vitro and in vivo. (bloodjournal.org)
  • The Streptococcus pneumoniae capsule is vital for virulence and may inhibit complement activity and phagocytosis. (asm.org)
  • APL-1 and APL-2, are derivatives of Compstatin, bind to and inhibit complement activation at the C3 level, thus blocking all major effector pathways of complement activation. (biomedcentral.com)
  • These pathways depend on different molecules for their initiation, but they converge to generate the same set of effector molecules ( Fig. 2.7 ). (nih.gov)
  • Since convertases mediate nearly all complement effector functions, they are ideal targets for therapeutic complement inhibition. (frontiersin.org)
  • All of these pathways generate a crucial enzymatic activity that, intern, generates the effector molecules of complement. (wikipathways.org)
  • Recent data have highlighted similarities between pathogen recognition, signaling pathways, and effector mechanisms of innate immunity in Drosophila and mammals, pointing to a common ancestry of these defenses. (sciencemag.org)
  • No matter, how the complement system is activated, generation of C5 convertase is important for the culmination of the complement mediated effector mechanisms, leading to the formation of Membrane Attack Complex (MAC). (epomedicine.com)
  • The complement system is designed to mobilize a large number of immune effector mechanisms when it detects infected or injured self tissues. (asmscience.org)
  • Complement C5a, like C3a is an anaphylatoxin, and is a chemotactic attractant for induction of neutrophilic release of antimicrobial proteases and oxygen radicals. (sigmaaldrich.com)
  • The underlying etiologies of MPGN comprise a spectrum of conditions including infection, monoclonal gammopathy, autoimmune or rheumatologic disease, and dysregulation of the alternative complement pathway. (hindawi.com)
  • Dysregulation of complement activity has, therefore, been connected to various diseases, including autoimmune conditions, thrombotic pathologies and infections. (els.net)
  • Complement dysregulation and deficiencies are connected to disease. (els.net)
  • Consequently, biomarkers of complement dysregulation may be useful for prediction or treatment of disease. (ahajournals.org)
  • Because renal damage with proteinuria is a characteristic pathological feature of preeclampsia, we hypothesized that complement markers in urine, rather than plasma, could better reflect complement dysregulation in disease. (ahajournals.org)
  • however, they did not distinguish preeclampsia from chronic hypertension, supporting our hypothesis that complement markers in urine, rather than plasma, better reflect complement dysregulation. (ahajournals.org)
  • These histological features are referred to as C3 glomerulonephritis and imply that dysregulation of the complement alternative pathway ( Fig. 1 ) is central to the pathophysiology of the disease. (biologists.org)
  • Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are two ultra-rare renal diseases characterized by fluid-phase dysregulation of C3 and C5 convertases that can lead to partial or complete consumption of circulating complement components, including C3. (uiowa.edu)
  • This nonproteolytically activated form of C3 can lead to the formation of the alternative pathway C3 convertase by interacting with factors B and D. This convertase formation can be further induced and stabilised by properdin. (els.net)
  • Instead to the other pathways and in addition to properdin as the initiating molecule, the alternative complement pathway (ACP) is activated via a low level of constitutive spontaneous hydrolysis of C3 in a process known as tick-over. (intechopen.com)
  • Factor B, factor D, and properdin (factor P) are specific components of the alternative pathway of complement activation. (asmscience.org)
  • C3b generates new C3 convertases by interacting with factors B, D and properdin. (uiowa.edu)
  • C3 convertase formation can occur in three different pathways: the classical, lectin, and alternative pathways. (wikipedia.org)
  • The activation of the complement system is initiated through three different pathways: the classical, the alternative, and the mannan-binding lectin (MBL) pathways. (asm.org)
  • The human complement system can be activated by three different pathways: the classical pathway, the lectin pathway, and the alternative pathway. (asnjournals.org)
  • The early step of complement system varies in different pathways. (microbeonline.com)
  • Human Complement C3 (C3) is synthesized as a single-chain pro-molecule (185 kDa) that then suffers several post-translational modifications. (adipogen.com)
  • In experimental sepsis, the blockade of complement anaphylatoxin C5a virtually prevented the appearance of MOF and improved the outcome [ 24 - 26 ]. (hindawi.com)
  • Pangburn and Rawal, 2002 ) to form a C5 convertase (C3bBb3b or C4b2a3b), which cleaves C5 to generate the large fragment C5b and the anaphylatoxin C5a ( Figure 1A ). (embopress.org)
  • Recombinant Human C3 N-terminal anaphylatoxin construct, aa. (arigobio.com)
  • The classical pathway is initiated by the binding of antibodies to cell surface antigens. (sigmaaldrich.com)
  • Monitoring patients with the C1q assay, which detects antibodies that fix complement, offers a minimally invasive means of identifying patients at risk for transplant glomerulopathy and graft loss. (labome.org)
  • 05). The results of our study suggest that anti-beta2GPI antibodies may play a role in GMT formation, and this process might involve complement activation. (labome.org)
  • 3 The majority of blood group antibodies (including both alloantibodies and autoantibodies) that can fix complement, however, activate complement up to the C3 stage but do not go on to act as hemolysins. (bloodjournal.org)
  • Immunological characterization of the cell-bound C3 fragments with monoclonal antibodies shows an evolution of the proteolysis of the fragments from iC3b to C3dg epitopes. (biochemj.org)
  • The complement system is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promotes inflammation, and attacks the pathogen's plasma membrane. (technologynetworks.com)
  • In the early 20th century, this controversy was resolved when it became understood that complement can act in combination with specific antibodies, or on its own in a non-specific way. (rhein-main-verzeichnis.info)
  • To elucidate which SCR domains are involved in abolishing complement-enhanced neutralization of vaccinia virus virions, we generated and characterized a panel of mouse monoclonal antibodies (MAbs) raised against VCP. (asm.org)
  • A complex of complement fragments C4b, C2a and C2b. (qmul.ac.uk)
  • Acts as complement inhibitor by disrupting the formation of the classical C3 convertase. (uniprot.org)
  • Anticomplementary activity of Boswellia acids--an inhibitor of C3-convertase of the classical complement pathway. (thefreedictionary.com)
  • A novel bifunctional chimeric complement inhibitor that regulates C3 convertase and formation of the membrane attack complex. (springer.com)
  • Blocking the terminal complement pathway with the C5 inhibitor eculizumab has revolutionized the clinical management of several complement-mediated diseases and has boosted the clinical development of new inhibitors. (onmedica.com)
  • Data on the C3 inhibitor Compstatin and the C5 inhibitors eculizumab and Coversin reported here demonstrate that C3/C5 convertases function differently from prevailing concepts. (onmedica.com)
  • Once C3b is formed - it can either follow alternative pathway or bind to C4bC2a (C3 convertase) to form C5 convertase. (epomedicine.com)
  • Three activation pathways converge at the formation of C3 convertases, cleaving C3 into C3a and C3b. (embopress.org)
  • Spontaneous hydrolysis of C3. (epomedicine.com)
  • However, a fluid‐phase AP C3 convertase C3(H 2 O)Bb can also assemble after spontaneous hydrolysis of the C3 thioester and initiate the AP ( Pangburn and Muller‐Eberhard, 1983 ). (embopress.org)
  • The complement system is pivotal in host defense but also contributes to tissue injury in several diseases. (nih.gov)
  • C3 plays a central role in the activation of the complement system. (abcam.com)
  • The complement system in B cell regulation. (springer.com)
  • It plays a central role in the complement system and contributes to innate immunity. (wikipedia.org)
  • Nowadays, this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation, and in the defense against pathogens. (frontiersin.org)
  • Nevertheless, it can be also an enemy, when pathogens hijack complement regulators to protect themselves from the immune system. (frontiersin.org)
  • Complement system represents a major part of the innate immunity. (frontiersin.org)
  • After that, for a long time, complement system has been considered as a supportive part of the innate immunity and received relatively little attention from the immunologists. (frontiersin.org)
  • Although initially thought to be predominantly important for host defense by aiding in Ab-mediated clearance of pathogens, it is now well appreciated that functions of the complement system extend to tissue homeostasis, immune response modulation, and elimination of unwanted or dying cells ( 5 , 6 ). (jimmunol.org)
  • In several models of autoimmune diseases, the overactivation of the complement system (CS) is the cause of disease exacerbation. (scielo.br)
  • Among its related pathways are Creation of C4 and C2 activators and Innate Immune System . (genecards.org)
  • Indeed, it now seems clear that complement first evolved as part of the innate immune system , where it still plays an important role. (nih.gov)
  • In the case of the complement system, the precursor zymogens are widely distributed throughout body fluids and tissues without adverse effect. (nih.gov)
  • There are three ways in which the complement system protects against infection. (nih.gov)
  • In our previous work, we developed a model system to form purified alternative pathway (AP) C5 convertases on C3b-coated beads and quantify C5 conversion via functional analysis of released C5a. (frontiersin.org)
  • Here, we developed a C3aR cell reporter system that enables functional discrimination between C3 and C5 convertases. (frontiersin.org)
  • The underlying immune response is highly complex and involves activation of the complement system as a crucial entity of innate immunity. (hindawi.com)
  • Uncontrolled activation of the complement system during sepsis and SIRS with in excessive generation of complement activation products contributes to an ensuing dysfunction of various organ systems. (hindawi.com)
  • As a central entity of innate immunity, the complement system is immediately activated after trauma or infection in order to control the replication of intruding pathogens. (hindawi.com)
  • Previous studies strongly suggest a mutual crosstalk between the complement and the coagulation system [ 27 - 30 ]. (hindawi.com)
  • Due to the complex nature of plasmatic cascades and their interconnections, the role and regulations of the complement system, especially in states of disease, are still inadequately understood. (hindawi.com)
  • This article is sought to provide insights into the pathogenesis of multiorgan failure associated with systemic inflammation with particular focus on the role of the complement system. (hindawi.com)
  • Complement is an important part of the innate immune system, which plays a primary role in protecting the host from infections ( 6 ). (jimmunol.org)
  • Complement is an evolutionary conserved system. (els.net)
  • Carroll MC (2004) The complement system in regulation of adaptive immunity. (els.net)
  • The complement system is an important mediator of the host immune response to infection and tissue damage, but may cause substantial injury when activated inappropriately. (bloodjournal.org)
  • 3 CRP elicits a multitude of effects on endothelial biology that favor a proatherosclerotic phenotype, such as decreasing NO release, 4 upregulating adhesion molecules, 5 stimulating vascular smooth muscle cell proliferation and migration, 6 and activating the complement system. (ahajournals.org)
  • Complement system is the pillar of the immune system by its dual role in homeostasis and disease. (intechopen.com)
  • Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway, and the lectin pathway. (technologynetworks.com)
  • Identification of membrane components of Trypanosoma cruzi modulators of complement system. (elsevier.com)
  • 2. Müller-Eberhard, H.J. Molecular organization and function of the complement system. (qmul.ac.uk)
  • Activation of the complement system occurs through multiple mechanisms that include three well-described pathways: the classical, lectin, and alternative complement activation pathways. (asm.org)
  • This chapter highlights the various roles of the complement system in the orchestration of the immune response towards microbial infections, gives examples of microbial strategies to evade complement-mediated clearance, and discusses how acquired and inherited complement deficiencies may predispose an organism to infectious disease. (asmscience.org)
  • Thus, complement constitutes the fundamental proinflammatory response system that can trigger and regulate the remainder of the immune response. (asmscience.org)
  • The complement system is the first line of immunological defense against foreign pathogens. (justia.com)
  • C4 plays a central role in the activation of the classical pathway of the complement system. (adipogen.com)
  • Each of the three pathways of the complement system results in the formation of C3 convertase on the pathogen surface. (davidson.edu)
  • The alternative complement pathway (AP) is an important nonantibody- requiring host defense system. (rice.edu)
  • We reported recently that the complement (C) system may play a role in the febrile response of guinea pigs to intravenous lipopolysaccharide (LPS) administration because C depletion abolished the LPS-induced rise in core temperature (T c ). (physiology.org)
  • C5 convertase, generated by the alternative, classical, or lectin pathway, initiates the activation of late components of the complement system to form membrane attack complex (MAC) and ultimately kills the pathogen. (microbeonline.com)
  • The capsule impaired bacterial opsonization with C3b/iC3b by both the alternative and classical complement pathways and also inhibited conversion of C3b bound to the bacterial surface to iC3b. (asm.org)
  • To prevent host cell damage, nucleated cells have developed membrane-bound regulators of complement activation. (ahajournals.org)
  • The Decay accelerating factor (DAF) inhibits C3 convertase. (wikipathways.org)
  • It inhibits complement activation at the yeast surface and, in addition, mediates adhesion of C. albicans to host endothelial cells. (labome.org)
  • It inhibits the formation of the alternative C3-convertase and accelerates its decay. (asnjournals.org)
  • This review highlights complement-mediated inflammation, and the mechanism through it triggers the airway tissue injury and remodeling in the airway epithelium that could serve as potential targets for developing a new drug to rescue the asthma patients. (biomedcentral.com)
  • C3-beta-c: Acts as a chemoattractant for neutrophils in chronic inflammation. (arigobio.com)
  • However, surface localization precludes detailed analysis of convertase activation and inhibition. (frontiersin.org)
  • Complement inhibition at the level of C3 or C5: mechanistic reasons for ongoing terminal pathway activity. (onmedica.com)
  • Overall, these data show that the S. pneumoniae capsule affects multiple aspects of complement- and neutrophil-mediated immunity, resulting in a profound inhibition of opsonophagocytosis. (asm.org)
  • This results in inhibition of the classical and lectin pathway of complement activation, probably due to interference with binding of C2a to C4b such that C3 convertase cannot be formed. (genecards.org)
  • Complement inhibition is an intriguing treatment option for patients with severe preeclampsia. (ahajournals.org)
  • The data support the need for further efficacy testing of targeting complement and/or its receptors to improve kidney transplant outcome in humans. (jci.org)
  • This gene is a member of the receptors of complement activation (RCA) family and is located in the 'cluster RCA' region of chromosome 1. (nih.gov)
  • Together, they form a 2 ligands -2 receptors pathway involved in the stimulation of B- and T-cell function and the regulation of humoral immunity. (string-db.org)
  • Complements C3a and C4b are opsonins that bridge phagocytes to microorganisms. (sigmaaldrich.com)
  • Furthermore, complement activation can result in formation of opsonins (C3b), promoting the engulfment of target cells by phagocytes. (bloodjournal.org)
  • alternative pathway-mediated amplification was evident at moderately low MBL/MASP concentrations but was not required at high MBL/MASP concentrations. (nih.gov)
  • The hydrolysis induces a conformational change that allows factor B to bind and form the alternative complement activation pathway C3 convertase (amplification loop is represented by the bold dotted arrow). (els.net)
  • Importantly, thanks to its amplification loop, ACP plays a major role for the final effect of initial specific activation of the classical and lectin complement pathways and contributed to 80-90% of any C5 activation regardless the initiating pathway [ 2 ]. (intechopen.com)
  • The results suggest that CRP bound to a surface provides secondary binding sites for H resulting in greater regulation of alternative pathway amplification and C5 convertases. (nih.gov)
  • Lastly, the alternative pathway is spontaneously activated leading to membrane attack complex formation in the absence of regulatory molecules ( 4 ). (jimmunol.org)
  • Both pathways lead to the formation of a common C3 convertase, an enzyme complex with serine proteinase trypsin‐like specificity. (els.net)
  • 1 The pathobiologic effects of complement are mediated directly by the formation of the cytolytic membrane attack complex (C5b-9), and indirectly by the generation of anaphylatoxins C3a and C5a. (bloodjournal.org)
  • Vascular endothelial growth factor receptor-1, interleukin-6 and TNF-alpha are all released by complement activation leading to angiogenesis with the formation of new blood vessels . (lecturio.com)
  • What are the two pathways of that can initiate phagocytosis? (brainscape.com)
  • DAF acts on C2b and Bb and dissociates them rapidly from C4b and C3b - thereby preventing the assembly of the C3 convertase. (wikipedia.org)
  • C2a, a serine protease, then combines with complement factor C4b to generate the C3 or C5 convertase. (uniprot.org)
  • The structures of the von Willebrand factor A and serine protease domains from human complement factor B ( P00751 ) have been analysed [ PMID: 15016353 , PMID: 10637221 ]. (ebi.ac.uk)
  • Generation of human C3 derivatives with CVF-like function for therapeutic complement depletion. (springer.com)
  • Synthetic peptide within Human C3 aa 1200-1300. (abcam.com)
  • Nephritic factor of the classical pathway of complement: immunoglobulin G autoantibody directed against the classical pathway C3 convertase enzyme. (uiowa.edu)
  • The smaller fragment called C3a serves to increase vascular permeability and promote extravasation of phagocytes, while the larger C3b fragment can be used as an opsonin or bind to either type of C3 convertase to form the trimolecular C5 convertase to activate C5 for the membrane attack complex. (wikipedia.org)
  • It also accelerates the degradation of the C4bC2a complex (C3 convertase) by dissociating the complement fragment C2a. (genecards.org)
  • The large fragment formed when COMPLEMENT C4 is cleaved by COMPLEMENT C1S. (labome.org)
  • In in vitro studies, we found that paclitaxel-treated rat neuronal cells activated complement, leading to cellular injury. (jimmunol.org)
  • Using an in vitro alloimmune incompatibility model, sCR1 inhibited complement activation and prevented hemolysis. (bloodjournal.org)
  • We further identified potential functional domains in CR1 that can act to limit complement-mediated RBC destruction in vitro and in vivo. (bloodjournal.org)
  • In in vitro complement assays, SUSD4 augments the alternative but not the classical pathway of complement activation at the C3 convertase step. (sinobiological.com)
  • In contrast, lectin pathway activation depends on the collectin family of molecules, including mannose-binding lectins (MBL) and ficolins. (jimmunol.org)
  • Complement factors C3a, C5a and C4 can induce vasodilatation, increased capillary permeability, and expression of leukocyte adhesion molecules. (sigmaaldrich.com)
  • A complex of complements C5b,C6, C7, and C8 mediates the polymerization of up to eighteen C9 molecules into a tube-like membrane attack complex that is inserted into the plasma membrane of an unwanted organism such as of gram-negative bacteria and viral infected cells. (sigmaaldrich.com)
  • Dotted black lines within the C3 and C3‐derived molecules indicate the presence of disulfide bonds. (els.net)
  • 4 Because of the contribution of complement in RBC destruction, we have taken the approach of activation using recombinant complement inhibitory molecules to block complement-mediated immune hemolysis, and thereby prevent some of its associated life-threatening effects. (bloodjournal.org)
  • Developmentally regulated expression by Trypanosoma cruzi of molecules that accelerate the decay of complement C3 convertases. (elsevier.com)
  • The lectin pathway is activated by carbohydrate recognition molecules that bind to polysaccharide on the surface of a pathogen. (asmscience.org)
  • Complement was discovered at the end of the nineteenth century and described as a "factor" or "principle" capable to induce bacterial lysis. (frontiersin.org)
  • Activation of C3 by complement pathway C3 convertases and its subsequent attachment to target surface leads to assembly of the membrane attack complex and ultimately to damage or lysis of the target cells. (justia.com)
  • Analytic study on the differential anticomplementary effects of dextran sulphate and heparin in the assay for the mouse alternative pathway. (thefreedictionary.com)
  • The seven remaining MAbs did not alter VCP function in the complement neutralization assay and recognized VCP bound to C3b/C4b. (asm.org)
  • The proteolysis appears to be fairly specific to C3, as C4, which also possesses an intramolecular thioester bond, is not cleaved and does not bind to the cells. (biochemj.org)
  • C4b and C2a bind to form C3-convertase. (adipogen.com)
  • Nonproteolytic activation can also occur by hydrolysis of the protected, unreactive thioester bond of native C3. (els.net)
  • Decay-accelerating factor (DAF) is another negative regulator of C3 convertase. (wikipedia.org)
  • Age-related macular degeneration and cancer will be described as examples showing that complement contributes to a large variety of conditions, far exceeding the classical examples of diseases associated with complement deficiencies. (frontiersin.org)
  • 2009) Complement in human diseases: Lessons from complement deficiencies. (els.net)
  • This body of literature, to be reviewed herein, suggests that complement components produced by the liver as well as by kidney cells and immune cells play crucial roles as pathogenic mediators of transplant rejection in animals and humans. (jci.org)
  • The complement mediators are the major effectors of the immune balance, which operates at the interface between the innate and adaptive immunity, and is vital for many immunoregulatory functions. (biomedcentral.com)
  • Anaphlatoxin is a substance produced by complement activation that causes the release of histamine and other mediators of immediate hypersensitivity from basophils and mast cells, thereby producing signs and symptoms of immediate hypersensitivity (anaphylaxis) without the involvement of IgE. (lecturio.com)
  • Kupffer cells and other macrophage cell types help clear complement-coated pathogens. (technologynetworks.com)
  • Membrane immune adherence receptor that plays a critical role in the capture and clearance of complement-opsonized pathogens by erythrocytes and monocytes/macrophages (PubMed:2963069). (nih.gov)
  • This review discusses recent advances in the understanding of the role of complement in physiology and pathology. (frontiersin.org)
  • However, the role of complement in CIPN remains unclear. (jimmunol.org)
  • Our findings demonstrate a previously unknown but pivotal role of complement in CIPN and suggest that complement may be a new target for the development of novel therapeutics to manage this painful disease. (jimmunol.org)
  • In this review, we discuss how studying CFHR5 nephropathy can contribute to our understanding of the role of complement in kidney diseases such as dense deposit disease, C3 glomerulonephritis and atypical haemolytic uraemic syndrome. (biologists.org)
  • We next discuss the role of complement in membranoproliferative glomerulonephritis (MPGN), dense deposit disease (DDD), C3 glomerulonephritis and atypical haemolytic uraemic syndrome (aHUS). (biologists.org)
  • Opportunities for new therapies based on the natural regulators of complement activation. (wikipathways.org)
  • As might be expected, there are many regulatory mechanisms to prevent uncontrolled complement activation. (nih.gov)

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